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BIOMARKER:

MET amplification

i
Other names: DFNB97, AUTS9, RCCP2, C-Met, HGFR, HGF Receptor, Met Proto-Oncogene, HGF/SF Receptor, Proto-Oncogene C-Met, Scatter Factor Receptor, Tyrosine-Protein Kinase Met, Hepatocyte Growth Factor Receptor, MET, MET Proto-Oncogene, Receptor Tyrosine Kinase
Entrez ID:
4d
Primary Enteric Adenocarcinoma Lung with Mesenchymal Epithelial Transition Factor Amplification: A Case Report. (PubMed, Gulf J Oncolog)
This is a rare case of PEAC with c-MET over expression. The MET axis that is implicated in pathogenesis of colonic adenocarcinomas might also be the molecular pathway for the development of PEAC.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NKX2-1 (NK2 Homeobox 1) • CDX-2
|
EGFR mutation • MET amplification • EGFR expression • ALK rearrangement • MET overexpression • MET expression
|
Savicol (valproic acid)
4d
CNS Dose Escalation/Expansion of Tepotinib in MET-driven NSCLC (clinicaltrials.gov)
P1/2, N=65, Not yet recruiting, Criterium, Inc. | Initiation date: Jul 2021 --> Mar 2022
Clinical • Trial initiation date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET fusion
|
Tepmetko (tepotinib)
5d
Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study. (PubMed, BMC Pulm Med)
In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.
Clinical • Journal
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
BRAF mutation • EGFR T790M • MET amplification • ALK rearrangement • EGFR exon 18 mutation • BRAF exon 15 mutation
6d
Next Generation Sequencing of Circulating Tumor DNA Can Optimize Second Line Treatment in RAS Wild Type Metastatic Colorectal Cancer after Progression on Anti-EGFR Therapy: Time to Rethink Our Approach. (PubMed, Oncol Res Treat)
The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic colorectal cancer and guide clinical decisions. NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.
Clinical • Review • Journal • Next-generation sequencing • Circulating tumor DNA
|
MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK (Neurotrophic receptor tyrosine kinase)
|
HER-2 amplification • BRAF mutation • MET amplification • RAS wild-type • HER-2 amplification + MET amplification
10d
Correlation of MET-Receptor Overexpression with MET Gene Amplification and Patient Outcome in Malignant Mesothelioma. (PubMed, Int J Mol Sci)
Our results imply that MET overexpression occurs in a substantial fraction of predominantly epithelioid MMs, but correlates poorly with MET-amplification status, and may impact the likelihood of response to mesothelioma standard chemotherapy. The predictive significance of MET-IHC and -FISH for possible MET-targeted therapy of MM remains to be elucidated.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET overexpression • MET exon 14 mutation • MET positive • MET expression • MET fusion
10d
Hepatocellular carcinoma patients with high circulating cytotoxic T cells and intra-tumoral immune signature benefit from pembrolizumab: results from a single-arm phase 2 trial. (PubMed, Genome Med)
Taken together, HCC patients with infiltration of cytotoxic T cells, along with increased active circulating CD8+ T cells during pembrolizumab treatment and down-regulation of neutrophil-associated markers, significantly benefited from pembrolizumab treatment.
Clinical • P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase) • CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD14
|
MET amplification • MET mutation • CTNNB1 mutation
|
Keytruda (pembrolizumab) • Nexavar (sorafenib)
10d
Nivolumab, Cabozantinib S-Malate, and Ipilimumab in Treating Patients With Recurrent Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov)
P2, N=169, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
Clinical • Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
EGFR L858R • MET amplification • EGFR exon 19 deletion • ALK rearrangement • MET exon 14 mutation • EGFR L861Q • RET rearrangement • EGFR G719X • EGFR negative • MET-H
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
12d
Savolitinib in Treating Patients With MET Amplified Metastatic or Unresectable Colorectal Cancer (clinicaltrials.gov)
P2, N=15, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
Clinical • Enrollment closed
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability)
|
MET amplification • KRAS wild-type • NRAS wild-type
|
Guardant360® CDx
|
Orpathys (savolitinib)
13d
EMB-01 in Patients With Advanced/Metastatic Gastrointestinal Cancers (clinicaltrials.gov)
P1/2, N=96, Recruiting, Shanghai EpimAb Biotherapeutics Co., Ltd.
Clinical • New P1/2 trial
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR expression • EGFR overexpression • MET overexpression
|
EMB-01
17d
PROGNOSTIC ROLE OF DRIVER GENETIC ALTERATIONS DETERMINED IN REAL-LIFE MOLECULAR TESTING ON 1,282 SARDINIAN PATIENTS WITH ADVANCED STAGE LUNG ADENOCARCINOMA (AIOM 2021)
Conclusions. In our study EGFR mutations represented the only independent factor, which impacted significantly on global survival of Sardinian patients with advanced adenocarcinoma, regardless of the treatment received, or the age, sex and smoking status.
Clinical • IO biomarker
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • BRAF mutation • MET amplification • ALK rearrangement
17d
MOLECULAR CHARACTERIZATION OF EPIDERMAL GROWTH FACTOR RECEPTOR-MUTATED (EGFR-M) NON-SMALL CELL LUNG CANCER (NSCLC) UNDERGOING HISTOLOGICAL TRANSFORMATION (AIOM 2021)
Histological and molecular evaluations are complementary in studying EGFR-TKI acquired resistance. NGS analyses in plasma might correlate with the risk of histological transformation and open new treatment perspectives.
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1)
|
TP53 mutation • EGFR mutation • EGFR T790M • MET amplification • EGFR exon 19 deletion • EGFR amplification • MYC amplification • CBL mutation
|
Oncomine™ Comprehensive Assay v3M
19d
Molecular characterization and clinical outcomes in EGFR-mutant de novo MET-overexpressed advanced non-small-cell lung cancer. (PubMed, ESMO Open)
Our findings provided clinical evidence that patients with concurrent EGFR sensitizing mutation and de novo MET amplification/overexpression could benefit from first-line EGFR-TKI monotherapy.
Clinical • Clinical data • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR overexpression • MET overexpression • MET mutation
|
Xalkori (crizotinib)
19d
Anticancer drug resistance: An update and perspective. (PubMed, Drug Resist Updat)
Resistance to adagrasib, an experimental antitumor agent exerting its cytotoxic effect as a covalent inhibitor of the G12C KRas, indicated that half of the cases present multiple KRas mutations as well as allele amplification...These vastly important and tantalizing questions in drug discovery, and broadly in precision medicine, are the focus of our present review. We end with our perspective, which calls for target combinations to be selected and prioritized with the help of the emerging massive compute power which enables artificial intelligence, and the increased gathering of data to overcome its insatiable needs.
Review • Journal
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1)
|
KRAS mutation • BRAF mutation • NRAS mutation • KRAS G12C • MET amplification • PTEN mutation • RET fusion • ALK fusion • NF1 mutation • RET mutation • KRAS G12 • FGFR3 fusion • BRAF amplification
|
adagrasib (MRTX849)
19d
Landscape and Clonal Dominance of Co-occurring Genomic Alterations in Non-Small-Cell Lung Cancer Harboring MET Exon 14 Skipping. (PubMed, JCO Precis Oncol)
METex14 mutations frequently co-occur with other potential driver oncogenes with differing patterns of clonal dominance observed among the drivers. This cellular context can provide insights into whether METex14 is acting as a primary oncogenic driver or resistance mechanism and help guide treatment choices.
Journal
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • CCDC6 (Coiled-Coil Domain Containing 6)
|
EGFR mutation • PIK3CA mutation • MET amplification • PTEN mutation • RET fusion • MET exon 14 mutation • MET mutation • EGFR mutation + PTEN mutation
|
Xalkori (crizotinib)
27d
INSIGHT 2: a Phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance. (PubMed, Future Oncol)
The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov).
Clinical • P2 data • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification
|
Tagrisso (osimertinib) • Tepmetko (tepotinib)
28d
FLOWERS: Osimertinib With or Without Savolitinib as 1L in de Novo MET+, EGFR+ NSCLC (clinicaltrials.gov)
P2, N=44, Not yet recruiting, Guangdong Association of Clinical Trials
Clinical • New P2 trial
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET overexpression • MET expression • MET-H
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
1m
MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small cell lung cancer. (PubMed, Future Oncol)
In the ongoing CHRYSALIS study (NCT02609776), amivantamab in combination with lazertinib, a potent, brain-penetrant third-generation EGFR TKI, demonstrated antitumor activity in the treatment-naïve and osimertinib-relapsed setting. Here the authors present the methodology for the MARIPOSA study (NCT04487080), a phase 3, multicenter, randomized study designed to compare the efficacy and safety of amivantamab and lazertinib combination therapy versus single-agent osimertinib as first-line treatment for EGFR-mutant non-small cell lung cancer.
Clinical • P3 data • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET mutation
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
1m
SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov)
P2, N=259, Recruiting, AstraZeneca | Trial primary completion date: Feb 2022 --> Sep 2022
Clinical • Trial primary completion date
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR amplification • MET overexpression
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
1m
Tepotinib in Patients with Advanced NSCLC with MET Amplification (METamp) (MTCS 2021)
In the first study of a MET inhibitor in advanced NSCLC with MET amp prospectively detected by LBx, tepotinib had high and clinically meaningful activity, especially in 1L, and was generally well tolerated. Tepotinib warrants further evaluation in advanced NSCLC with MET amp.
Clinical
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
|
Guardant360® CDx
|
Tepmetko (tepotinib)
1m
Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics. (PubMed, Onco Targets Ther)
This review outlines the clinical data supporting capmatinib approval in the treatment of NSCLC and FoundationOne CDx approval as a companion diagnostic. We detail the practical clinical administration of capmatinib, including dosing and toxicity management, compare capmatinib to other approved and investigational MET-targeted therapies, discuss limitations of capmatinib, and highlight ongoing trials of capmatinib in combinatorial approaches.
Journal • Review • Companion diagnostic
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation
|
FoundationOne® CDx
|
Tabrecta (capmatinib)
1m
A Study of Amivantamab in People With Esophagogastric Cancer (clinicaltrials.gov)
P2, N=25, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting
Enrollment open
|
HER-2 (Human epidermal growth factor receptor 2)
|
MET amplification • EGFR amplification
|
Rybrevant (amivantamab-vmjw)
2ms
Real-World Approach for Molecular Analysis of Acquired EGFR Tyrosine Kinase Inhibitor Resistance Mechanisms in NSCLC. (PubMed, JTO Clin Res Rep)
With the approval of first-line osimertinib treatment in stage IV EGFR-mutated NSCLC, detection of resistance mechanisms will become increasingly important-and complex...In case of financial or tissue limitations, a sequential approach is justifiable, in which RNA NGS is only performed in case no resistance mechanisms are identified. Yet, this is suboptimal as-although rare-multiple acquired resistance mechanisms may occur.
Clinical • Journal • Real-world evidence
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 amplification • MET amplification • HER-2 amplification + MET amplification
|
Tagrisso (osimertinib)
2ms
SACHI: Study on Savolitinib Combined With Osimertinib in Treatment of Advanced NSCLC With MET Amplification (clinicaltrials.gov)
P3, N=250, Recruiting, Hutchison Medipharma Limited | Not yet recruiting --> Recruiting | Initiation date: Aug 2021 --> Nov 2021
Clinical • Enrollment open • Trial initiation date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification
|
cisplatin • Tagrisso (osimertinib) • carboplatin • pemetrexed • Orpathys (savolitinib)
2ms
The natural product berberine synergizes with osimertinib preferentially against MET-amplified osimertinib-resistant lung cancer via direct MET inhibition. (PubMed, Pharmacol Res)
MET kinase assay showed clear concentration-dependent inhibitory effects of berberine against MET activity, confirming its kinase inhibitory activity. These findings collectively suggest that berberine can act as a naturally-existing MET inhibitor to synergize with osimertinib in overcoming osimertinib acquired resistance caused by MET amplification.
Journal
|
EGFR (Epidermal growth factor receptor) • MCL1 (Myeloid cell leukemia 1)
|
EGFR mutation • EGFR T790M • MET amplification
|
Tagrisso (osimertinib)
2ms
Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non-small-cell lung cancer. (PubMed, ESMO Open)
Emerging data also demonstrate MET amplification as a resistance driver to TKI-treated ALK-, RET-, and ROS-1-fusion NSCLC, consistently at the range of 15%, while the resistance profiling data are maturing for other molecular targets. In this review, we discuss MET amplification as a driver of acquired resistance in well-defined molecular subsets of NSCLC, explore the biology behind this mechanism of resistance, and summarize the recently published clinical data, including the proposed combination strategies in the clinic achieving success in overcoming acquired MET amplification-dependent resistance.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
EGFR mutation • MET amplification • EGFR amplification • ROS1 fusion
2ms
A Study of RC48-ADC in Subjects With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=36, Active, not recruiting, RemeGen Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2021 --> May 2022
Clinical • Enrollment closed • Trial completion date
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 overexpression • EGFR T790M • MET amplification • HER-2 mutation • MET mutation • HER-2 exon 20 mutation
|
Aidixi (disitamab vedotin)
2ms
New P2 trial
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
HER-2 positive • MET amplification
|
spartalizumab (PDR001) • Tabrecta (capmatinib)
2ms
Study of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal Cancer (PERSPECTIVE) (clinicaltrials.gov)
P2, N=48, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting
Clinical • Enrollment closed • Preclinical
|
BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • BRAF wild-type
|
Erbitux (cetuximab) • Tepmetko (tepotinib)
2ms
Oncocytic renal neoplasms with diffuse keratin 7 immunohistochemistry harbor frequent alterations in the mammalian target of rapamycin pathway. (PubMed, Mod Pathol)
At a median follow-up of 68 months (2-147 months) for 15 patients, all were alive without disease. Oncocytic renal tumors with diffuse keratin 7 labeling show frequent alterations in the TSC/MTOR pathway, despite more oncocytoma-like morphology than initially described in LOT, likely expanding the morphologic spectrum of the latter.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • STK11 (Serine/threonine kinase 11) • CDH1 (Cadherin 1) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • EPCAM (Epithelial cell adhesion molecule) • FOXP1 • KRT7 (Keratin-7) • PAX8 (Paired box 8) • MME (Membrane metallo-endopeptidase)
|
MET amplification • STK11 mutation • TSC1 mutation • MTOR mutation • TSC2 mutation • FGFR3 amplification • TSC1 deletion • PAX8 positive • TSC1 deletion
2ms
An updated patent review of small-molecule c-Met kinase inhibitors (2018-present). (PubMed, Expert Opin Ther Pat)
Most recent patents have focused on addressing the direction of c-Met amplification and overexpression. Despite the great success in the development of selective c-Met inhibitors, the effects of bypass secretion and mutagenesis have led to a need for new c-Met small molecule inhibitors that are safe, efficient, selective and less toxic with novel structures and effective against other targets.
Review • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • HGF (Hepatocyte growth factor)
|
MET amplification • MET overexpression • MET expression
2ms
[VIRTUAL] Clinical Implication of Persistent Positive ALK Status in Lung Cancer: Analysis of 18 Cases (AMP 2021)
Introduction : Since approval of an ALK fluorescence in situ hybridization (FISH) by the FDA as a champion diagnostic test to assist in identifying patients for targeted therapy with the first ALK inhibitor crizotinib in 2011, the assay has been used for more than 6,000 lung cancer cases in the Clinical Cytogenetics Laboratory at MD Anderson Cancer Center... Persistent positive ALK status obtained prior to, during, and/or after ALK inhibition likely has different implications. Necessary adjustment of clinical management will hopefully improve outcome of lung cancer patients.
Clinical
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4)
|
MET amplification • ALK positive • EML4-ALK fusion • ALK fusion • RET rearrangement • ROS1 rearrangement
|
Xalkori (crizotinib)
2ms
MET Amplification and Efficacy of Nivolumab in Patients With NSCLC. (PubMed, JTO Clin Res Rep)
MET amplification was not associated with greater benefit of nivolumab treatment in patients with NSCLC. Further studies are warranted to prioritize immune checkpoint inhibitors in the treatment regimen for patients with MET amplification.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
Opdivo (nivolumab)
2ms
Complete Response to Adjuvant Tepotinib in A Patient with Newly Diagnosed Disseminated Glioblastoma (GBM) Harboring MET Amplification (SNO 2021)
He completed proton craniospinal irradiation at 3600cGy followed by boost to the tumor bed at 2400cGy without concurrent temozolomide (TMZ) due to the large radiation field. Trials of targeted therapy in molecularly-unselected GBM have been largely disappointing, however, this case demonstrates the promise of targeting MET using tepotinib in GBM. A clinical trial of tepotinib in MET-amplified GBM and NSCLC brain metastasis is currently underway at MD Anderson.
Clinical
|
MET (MET proto-oncogene, receptor tyrosine kinase) • MGMT (6-O-methylguanine-DNA methyltransferase)
|
MET amplification • MET exon 14 mutation
|
temozolomide • Tepmetko (tepotinib)
2ms
Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS (LUMOS) study (SNO 2021)
Thes findings support moving to a larger study using contemporaneous and longitudinal tissue samples matched with targeted therapies as part of a comprehensive umbrella study design. Delivery and interpretation of molecular data is a challenge shared across oncology which may be mitigated with a neuro-oncology specific molecular tumor board.
NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR (Fibroblast Growth Factor Receptor) • CDK4 (Cyclin-dependent kinase 4) • MTAP (Methylthioadenosine Phosphorylase) • CCND3 (Cyclin D3)
|
MET amplification • MET fusion
2ms
PERSPECTIVE: Tepotinib + cetuximab for RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC) and acquired resistance to anti-EGFR antibody therapy due to MET amplification (METamp) (NCRI 2021)
Tepotinib (a highly selective, potent MET inhibitor) + gefitinib has shown improved progression-free survival (PFS; 16.6 vs 4.2 months; hazard ratio [HR]=0.13) and overall survival (OS; 37.3 vs 13.1 months; HR=0.08) in 19 pts with EGFR-mutant METamp NSCLC and acquired EGFR tyrosine kinase inhibitor resistance versus chemotherapy (INSIGHT: NCT01982955). No formal statistical hypothesis will be tested in this exploratory study. Results N/A Conclusion N/A Impact statement The dual approach of MET inhibition (tepotinib) plus an anti-EGFR (cetuximab) targeting MET pathway activation and maintaining EGFR pathway inhibition may provide a new treatment option for patients with mCRC and acquired resistance to anti-EGFR antibody therapy due to METamp.
Preclinical
|
BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
Erbitux (cetuximab) • gefitinib • Tepmetko (tepotinib)
2ms
MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors. (PubMed, Exp Hematol Oncol)
MET amplification identified by FISH remains the optimal biomarker to identify suitable candidates for MET-TKI therapy. In comparison, amplification identified by NGS seems not as robust to be effective predictive biomarker. Further exploration is needed regarding the focal amplification by NGS in predicting the efficacy.
Clinical • Journal • Next-generation sequencing
|
EGFR (Epidermal growth factor receptor)
|
MET amplification
2ms
A Study of Amivantamab in People With Esophagogastric Cancer (clinicaltrials.gov)
P2, N=25, Not yet recruiting, Memorial Sloan Kettering Cancer Center
New P2 trial
|
HER-2 (Human epidermal growth factor receptor 2)
|
MET amplification • EGFR amplification
|
Rybrevant (amivantamab-vmjw)
2ms
SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov)
P2, N=259, Recruiting, AstraZeneca | Trial completion date: Apr 2023 --> Sep 2022
Clinical • Trial completion date
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR amplification • MET overexpression
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
2ms
Comparison of MET gene amplification analysis by next-generation sequencing and fluorescence in situ hybridization. (PubMed, Oncotarget)
Therefore, for the assessment of MET amplifications using the QIAGEN NGS workflow, we suggest detecting amplified cases with an FC value of ≥ 3.0 and a CN value of ≥ 20.0 by FISH. In summary, NGS allows for DNA- and RNA-based analysis of specific MET gene amplifications, point mutations or rearrangements.
Journal • Next-generation sequencing
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • EGFR amplification
2ms
Effect of mesenchymal-epithelial transition amplification on immune microenvironment and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer. (PubMed, Ann Transl Med)
Gene set enrichment analysis (GSEA) results indicated significant up-regulation of the immune response-related pathways in the MET-amplification group. Our results suggest that MET amplification may be a novel predictive marker for immunotherapy efficacy in NSCLC.
Clinical • Journal • Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET-H
2ms
Clinical • Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR T790M negative
|
cisplatin • Tagrisso (osimertinib) • carboplatin • pemetrexed • Tabrecta (capmatinib)
2ms
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
tivantinib (ARQ 197)
3ms
Geometry-N: Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC (clinicaltrials.gov)
P2, N=38, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting | Trial completion date: Mar 2028 --> Sep 2028 | Initiation date: Sep 2021 --> Dec 2021 | Trial primary completion date: Mar 2023 --> Sep 2023
Clinical • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation
|
Tabrecta (capmatinib)
3ms
REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=111, Recruiting, Regeneron Pharmaceuticals | Trial completion date: Nov 2023 --> Oct 2024 | Trial primary completion date: Nov 2023 --> Oct 2024
Clinical • Trial completion date • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation • MET expression
|
REGN5093
3ms
Comprehensive Genomic Profiling of Circulating Cell-Free DNA Distinguishes Focal MET Amplification from Aneuploidy in Diverse Advanced Cancers. (PubMed, Curr Oncol)
Focal MET amp accounted for ~30% of all MET amp, which was found in 3.7% of patients with diverse cancers and was associated with a higher plasma copy number. Clinical studies are warranted to assess the clinical utility of targeted therapies for tumors with focal MET amplification detected by NGS of cfDNA.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
|
Guardant360® CDx
3ms
Mesenchymal-Epithelial Transition Exon 14 Skipping Mutation and Amplification in 5,008 Patients With Lung Cancer. (PubMed, Front Oncol)
Moreover, various splicing site changes at the DNA level led to the exon 14 skipping mutation at the mRNA level. Further studies are required to clarify the association between MET genomic alterations and prognosis.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
BRAF V600E • EGFR mutation • BRAF V600 • EGFR L858R • MET amplification • EGFR exon 19 deletion • MET exon 14 mutation
3ms
Resistance mechanisms to osimertinib and emerging therapeutic strategies in nonsmall cell lung cancer. (PubMed, Curr Opin Oncol)
The resistance mechanisms to osimertinib are heterogeneous and gradually perfected. The combination of osimertinib with bypass targeted therapy and other therapeutic approaches emerge as promising strategies.
Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 amplification • MET amplification • EGFR exon 20 insertion • EGFR C797S • MET mutation • EGFR exon 20 mutation • BCL2L11 deletion
|
Tagrisso (osimertinib)
3ms
MET Amplification in Non-Small Cell Lung Cancer (NSCLC)-A Consecutive Evaluation Using Next-Generation Sequencing (NGS) in a Real-World Setting. (PubMed, Cancers (Basel))
Cases harboring a MET GCN > 10 showed the best concordance when comparing FISH versus NGS (80%). This study confirms that an amplicon-based NGS assessment of the MET GCN detects high-level MET amplified cases harboring a MET GCN > 10 but fails to detect the various facets of MET gene amplification in the context of a therapy-induced resistance mechanism.
Clinical • Journal • Real-world evidence • Next-generation sequencing
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
3ms
Evolution of MET and NRAS gene amplification as acquired resistance mechanisms in EGFR mutant NSCLC. (PubMed, NPJ Precis Oncol)
Analysis of downstream signaling revealed extracellular signal-related kinase activation that could only be eliminated by trametinib treatment, while Akt activation could be modulated by various combinations of MET, EGFR, and PI3K inhibitors. The combination of an EGFR inhibitor with a MEK inhibitor was identified as a possible treatment option to overcome drug resistance related to NRAS gene amplification.
Preclinical • Journal
|
EGFR (Epidermal growth factor receptor) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • NRAS amplification
|
Mekinist (trametinib)
3ms
MET Gene High Copy Number (Amplification/Polysomy) Identified in Melanoma for Potential Targeted Therapy. (PubMed, Am J Clin Pathol)
In our study, MET gene amplification was identified in 11% of melanomas and is relatively concordant with few reported studies. However, about 26% of the additional melanoma cases showed MET gene polysomy, which has not been reported as per our knowledge. If these results are validated with further orthogonal studies, more of the melanoma cases could potentially benefit from targeted therapy with MET tyrosine kinase inhibitors.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
4ms
Genetic evolution to tyrosine kinase inhibitory therapy in patients with EGFR-mutated non-small-cell lung cancer. (PubMed, Br J Cancer)
At a given point and under selective TKI pressure, a single metastasis biopsy in disseminated tumours from EGFR-mutated NSCLC patients could provide a reasonable assessment of actionable alterations useful for therapeutic decisions.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • MET amplification
4ms
SPACEWALK: A Remote Participation Study of ALK Resistance Leveraging Plasma Cell-Free DNA Genotyping. (PubMed, JTO Clin Res Rep)
Through the leveraging of remote participation, plasma NGS offers an optimal mechanism for characterizing resistance to emerging targeted therapies in rare cancer populations, though sensitivity depends on adequate tumor DNA samples. Repeat cfDNA analysis on therapy may offer an objective monitoring approach to remotely study treatment response.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • ALK positive • ALK fusion • ALK mutation
4ms
Afatinib as a Potential Therapeutic Option for Patients With NSCLC With EGFR G724S. (PubMed, JTO Clin Res Rep)
In the subset who had progressed on osimertinib, afatinib also yielded a superior progression-free survival (6.2 mo) than non-afatinib therapies (1.0 mo, HR = 0.04, p = 0.005) and alternative EGFR TKIs (1.8 mo, HR = 0.06, p = 0.033). EGFR G724S emerges as a resistant mutation against EGFR TKI preferentially in the context of a rare variant of 19del, whereas it might mediate differential mechanisms in the context of exon 20 mutation. We also found that afatinib could be a potential therapeutic option for patients with NSCLC with G724S.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR exon 21 mutation • EGFR S768I • EGFR exon 20 mutation • EGFR E746_S752delinsV • EGFR G724S • EGFR E746
|
Gilotrif (afatinib) • Tagrisso (osimertinib)
4ms
Clinical • Late-breaking abstract
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation • MET-H
|
Tabrecta (capmatinib)
4ms
Targeting BRAF Activation as Acquired Resistance Mechanism to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small-Cell Lung Cancer. (PubMed, Pharmaceutics)
In this review, we discuss the rationale for EGFR/BRAF/MEK co-inhibition in the light of a clinical case of EGFR-mutant NSCLC developing a BRAF V600 mutation as an acquired resistance mechanism to osimertinib and responding to the association of osimertinib plus dabrafenib and trametinib. Additionally, we discuss the acquired resistance mechanisms to osimertinib plus dabrafenib and trametinib combination in that context.
Preclinical • Review • Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • BRAF mutation • BRAF V600 • MET amplification • EGFR C797S • PD-L1 amplification • BRAF amplification
|
Mekinist (trametinib) • Tagrisso (osimertinib) • Tafinlar (dabrafenib)
4ms
Clinical • Enrollment open • Combination therapy
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR T790M negative
|
cisplatin • Tagrisso (osimertinib) • carboplatin • pemetrexed • Tabrecta (capmatinib)
4ms
Clinical • New P2 trial
|
MET (MET proto-oncogene, receptor tyrosine kinase) • PIAS4 (Protein Inhibitor Of Activated STAT 4)
|
MET amplification • MET exon 14 mutation • MET mutation
|
Cabometyx (cabozantinib tablet)
4ms
Editorial: Global Regulatory Initiatives Deliver Accelerated Approval of the First Bispecific Therapeutic Monoclonal Antibody for Advanced Non-Small Cell Lung Cancer (NSCLC). (PubMed, Med Sci Monit)
"In 2019, Project Orbis was launched by the FDA Oncology Center of Excellence as a global collaborative review program to facilitate rapid global access for patients to innovative cancer therapies. This Editorial aims to highlight how global regulatory initiatives from the FDA have delivered accelerated approval of the first bispecific therapeutic monoclonal antibody, amivantamab-vmjw (Rybrevant®), and a companion diagnostic for patients with advanced NSCLC with an EGFR exon 20 insertion."
Journal • Clinical
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR exon 20 insertion • MET mutation • EGFR exon 20 mutation
|
Guardant360® CDx
|
Rybrevant (amivantamab-vmjw)
4ms
Tepotinib With Gefitinib in Participants With Locally Advanced or Metastatic NSCLC (INSIGHT) (clinicaltrials.gov)
P1/2, N=88, Completed, Merck KGaA, Darmstadt, Germany | Active, not recruiting --> Completed
Clinical • Trial completion • Preclinical
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET overexpression • EGFR T790M negative
|
cisplatin • gefitinib • carboplatin • pemetrexed • Tepmetko (tepotinib)
4ms
The Significance of MET Expression and Strategies of Targeting MET Treatment in Advanced Gastric Cancer. (PubMed, Front Oncol)
MET expression was examined immunohistochemically before and after treatment in 122 patients with unresectable or recurrent GC, and was evaluated according to H-score or the scoring criteria used in the MetMAb trial. MET expression is altered post chemotherapy and MET status should be evaluated in real-time. Both MET and pMET expressions might need to be considered for patients suitable for volitinib treatment.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
HER-2 overexpression • MET amplification • MET overexpression • MET expression • MET overexpression + HER-2 overexpression
|
Orpathys (savolitinib) • onartuzumab (RG3638)
4ms
Combination treatment with trastuzumab and crizotinib in metastatic gastric cancer harboring Her-2 amplification and c-MET amplification: A case report. (PubMed, Medicine (Baltimore))
The present case suggested that combinational therapy with trastuzumab and crizotinib might be effective in metastatic gastric cancer patients harboring Her-2 and c-MET amplification, even with a poor PS. It was also implied that gene sequencing might be valuable, especially in patients with limited treatment strategies.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
HER-2 amplification • MET amplification
|
Herceptin (trastuzumab) • Xalkori (crizotinib)
4ms
Mixed responses to first-line alectinib in non-small cell lung cancer patients with rare ALK gene fusions: A case series and literature review. (PubMed, J Cell Mol Med)
Both patients demonstrated improved survival after they switched to second-line crizotinib (PFS: 11 months) and ensartinib (PFS: 18 months), respectively, up till the last follow-up assessment. This study and literature review results showed mixed responses to alectinib in NSCLC patients who harboured rare ALK fusions. Comprehensive molecular profiling of tumour is thus strongly warranted for precise treatment strategies.
Clinical • Review • Journal
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • STRN (Striatin)
|
MET amplification • ALK positive • ALK rearrangement • ALK fusion • STRN-ALK fusion
|
Xalkori (crizotinib) • Alecensa (alectinib) • Ensacove (ensartinib)
4ms
Patient-relevant results in patients with METex14-mutated advanced NSCLC treated with capmatinib: Results from the phase 2 study GEOMETRY mono-1 (DGHO 2021)
QLQ-LC13 symptoms improved at all cycles in patients achieving clinical complete response or partial response, while symptom worsening was seen in those with no clinical response. Capmatinib was associated with clinically meaningful improvements in cough, delayed time to lung symptom deterioration, and preserved QoL, supporting its use as a treatment option in patients with METex14-mutated NSCLC.
Clinical • P2 data
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET mutation
|
Tabrecta (capmatinib)
4ms
Clinical • Enrollment change
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR exon 20 insertion • MET exon 14 mutation • EGFR C797S • MET mutation • EGFR exon 20 mutation • MET expression
|
carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
4ms
SHP2 as a Potential Therapeutic Target in Diffuse-Type Gastric Carcinoma Addicted to Receptor Tyrosine Kinase Signaling. (PubMed, Cancers (Basel))
Moreover, SHP2 knockdown or pharmacological inhibition blocked the migration and invasion of Met-addicted DGC cells in vitro and their peritoneal dissemination in a mouse xenograft model. These results indicate that SHP2 is a critical regulator of the malignant progression of RTK-addicted DGC and may be a therapeutic target.
Journal
|
FGFR2 (Fibroblast growth factor receptor 2)
|
MET amplification • FGFR2 amplification
4ms
RET Inhibitors in Non-Small-Cell Lung Cancer. (PubMed, Cancers (Basel))
Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
|
EGFR mutation • MET amplification • RET fusion • RET rearrangement • MET mutation • RET positive
|
lenvatinib • Cabometyx (cabozantinib tablet) • Retevmo (selpercatinib) • Caprelsa (vandetanib) • Gavreto (pralsetinib)
4ms
Correlation between PD-L1 expression and MET gene amplification in patients with advanced non-small cell lung cancer and no other actionable oncogenic driver. (PubMed, Oncotarget)
In conclusion, a positive correlation was found between MET gene amplification and PD-L1 expression and highly expressed (above 50%) in patients with NSCLC and no other actionable oncogenic driver. It could be translated as new guided-treatment oportunities for these patients.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • PD-1 (Programmed cell death 1)
|
PD-L1 expression • PD-L1 overexpression • MET amplification • MET expression
4ms
Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation. (PubMed, J Neurooncol)
While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • STAT3 (Signal Transducer And Activator Of Transcription 3)
|
EGFR mutation • MET amplification • EGFR amplification • EGFRvIII mutation
|
Avastin (bevacizumab) • Tagrisso (osimertinib) • temozolomide
4ms
Volitinib in Treating Patients With Recurrent or Refractory Primary CNS Tumors (clinicaltrials.gov)
P1, N=50, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2021 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2023
Clinical • Trial completion date • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET mutation • MET fusion • HGF amplification
|
Orpathys (savolitinib)
4ms
Characterization of Non-Small-Cell Lung Cancers With MET Exon 14 Skipping Alterations Detected in Tissue or Liquid: Clinicogenomics and Real-World Treatment Patterns. (PubMed, JCO Precis Oncol)
Diverse METex14 alterations were present in 2%-3% of NSCLC cases. Tissue and liquid comparisons showed high concordance and similar coalteration profiles. Characterizing common co-occurring alterations and immunotherapy biomarkers, including those present before or acquired after treatment, may be critical for predicting responses to MET inhibitors and informing rational combination strategies.
Clinical • Journal • HEOR • Real-world evidence • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
|
PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • MET amplification • HER-2 mutation • MET exon 14 mutation • TMB-L • CDK4 amplification
5ms
Savolitinib for Treating Gastric Cancer and Esophagogastric Junction Adenocarcinoma Patients (clinicaltrials.gov)
P2, N=75, Recruiting, Hutchison Medipharma Limited | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
Orpathys (savolitinib)
5ms
[VIRTUAL] Copy number variation detection for the indication of targeted ther- apy in a lung cancer patients series. Next-Generation Sequencing panel vs fluorescent in-situ hybridization (ECP 2021)
NGS panel increases the percentage of NSCLC patients suitable for a target therapy as it screens 52 genes in one single assay. ERBB2 and MET FISH assay performs better than the NGS panel as it is capable to detect CNV when less than ten copies of the gene or when heterogeneity of CNVs are present in tumour cells. NGS and FISH assay have the same accuracy in the detection of CNVs of MYC, FGFR1, CCND1 and EGFR.
Clinical • Next-generation sequencing
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR1 (Fibroblast growth factor receptor 1) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • CDK6 (Cyclin-dependent kinase 6)
|
HER-2 amplification • MET amplification
5ms
Dramatic response to osimertinib combined with crizotinib in EGFR T790 M mutation only in blood and Met amplification only in tumor tissue expressive non-small cell lung cancer: A case report. (PubMed, Medicine (Baltimore))
Although osimertinib combined with crizotinib therapy showed dramatic tumor shrinkage in both the primary tumor and bone metastasis to an EGFR T790M-mutant NSCLC patient with MET amplification, the progression-free survival (PFS) was only two months.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • EGFR T790M • MET amplification • MET mutation
|
Xalkori (crizotinib) • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib
5ms
Phase 1 Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody-Drug Conjugate Targeting c-Met, Monotherapy in Patients With Advanced Non-Small Cell Lung Carcinoma. (PubMed, Clin Cancer Res)
Teliso-V monotherapy was tolerated and showed antitumor activity in c-Met+ NSCLC. On the basis of overall safety, pharmacokinetics, and efficacy outcomes, 1.9 mg/kg Teliso-V Q2W and 2.7 mg/kg Q3W schedules were selected for further clinical development.
Clinical • P1 data • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
|
telisotuzumab vedotin (ABBV-399)
5ms
Clinical utility of next-generation sequencing-based ctDNA testing for common and novel ALK fusions. (PubMed, Lung Cancer)
Our findings support a complementary role for ctDNA in detection of ALK fusions and other alterations at diagnosis and therapeutic resistance settings.
Clinical • Journal • Next-generation sequencing • Circulating tumor DNA
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4) • CLTC (Clathrin Heavy Chain) • PON1 (Paraoxonase 1)
|
MET amplification • ALK fusion • ALK mutation • ALK G1202R • EML4-ALK G1202R
5ms
Real-world insights into patients with advanced NSCLC and MET alterations. (PubMed, Lung Cancer)
Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in older, METex14 patients who had more advanced disease at diagnosis. MET-targeted therapies could be beneficial in patients with these rare MET alterations.
Clinical • Journal • Real-world evidence • IO biomarker
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
5ms
Clinical • New P3 trial
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification
|
cisplatin • Tagrisso (osimertinib) • carboplatin • pemetrexed • Orpathys (savolitinib)
5ms
Traditional Chinese Medicine reverses resistance to epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer: a narrative review. (PubMed, J Tradit Chin Med)
Many resistance mechanisms of EGFR-TKIs in the treatment of non-small cell lung cancer still need to be explored. CHMs have great research potential in reversing the resistance to EGFR-TKIs.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog)
|
EGFR T790M • MET amplification • PTEN mutation • EGFR C797S • MET mutation • PTEN expression
5ms
New P1/2 trial
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • EGFR T790M • MET amplification • EGFR exon 19 deletion • EGFR amplification • EGFR exon 20 insertion • MET exon 14 mutation • EGFR C797S • MET mutation • EGFR exon 20 mutation
|
FoundationOne® CDx
|
MCLA-129
5ms
Circulating Tumor DNA Analysis Detects FGFR2 Amplification and Concurrent Genomic Alterations Associated with FGFR Inhibitor Efficacy in Advanced Gastric Cancer. (PubMed, Clin Cancer Res)
ctDNA sequencing identifies FGFR2 amplification missed by tissue testing in patients with advanced GC, and these patients may respond to FGFR inhibition. The utility of ctDNA sequencing warrants further evaluation to develop effective therapeutic strategies for patients with FGFR2-amplified advanced GC.
Clinical • Journal • Circulating tumor DNA
|
MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2)
|
MET amplification • FGFR2 amplification
5ms
Contrasting genomic profiles from metastatic sites, primary tumors, and liquid biopsies of advanced prostate cancer. (PubMed, Cancer)
CGP of PTs, MET sites, and ctDNA in PC exhibited differences most likely associated with tumor progression, clonal evolution, and exposure to systemic therapies; ctDNA can also capture a broad range of potential therapeutic opportunities for patients with PC.
Journal • Liquid biopsy • BRCA Biomarker • MSi-H Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • CDK12 (Cyclin dependent kinase 12) • ERG (ETS Transcription Factor ERG)
|
MSI-H/dMMR • HER-2 amplification • MET amplification • TMPRSS2-ERG fusion
5ms
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • KIF5B (Kinesin Family Member 5B)
|
MET amplification • MET fusion • MET D1228N • RET positive
|
Retevmo (selpercatinib) • Tabrecta (capmatinib)
5ms
KRAS inhibitor-resistance in MET-amplified KRAS non-small cell lung cancer induced by RAS- and non-RAS-mediated cell signaling mechanisms. (PubMed, Clin Cancer Res)
MET amplification leads to the development of resistance to KRAS inhibitors in NSCLC. Dual blockade of MET and KRAS could be a treatment option for MET amplified, KRAS -mutated NSCLC.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
KRAS mutation • MET amplification • KRAS amplification
|
Xalkori (crizotinib) • Lumakras (sotorasib)
5ms
Molecular profiling of soft-tissue sarcomas with FoundationOne Heme identifies potential targets for sarcoma therapy: a single-centre experience. (PubMed, Ther Adv Med Oncol)
In summary, FoundationOne Heme detected a broad range of genetic alterations and potential therapeutic targets in STS (e.g. HGF/MET in a subset of MFS, or PIK3CA in MLS). The assay's sensitivity for fusion detection was low in our sample and needs to be re-evaluated in a larger cohort.
Journal • Clinical
|
TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NF1 (Neurofibromin 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • KMT2C (Lysine Methyltransferase 2C) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2)
|
PIK3CA mutation • MET amplification • CDKN2A deletion • KMT2D mutation • MLL3 mutation
|
FoundationOne® Heme CDx
5ms
[VIRTUAL] Validation of Companion Diagnostics for the Identification of Patients with EGFR Exon20ins NSCLC for Amivantamab Therapy (IASLC-WCLC 2021)
Conclusion EGFR Exon20ins mutations identified by either plasma-based Guardant360CDx or tissue-based ODxT demonstrate the robust antitumor activity of amivantamab. Both tests provide accurate, comprehensive, and complementary approaches to identifying patients who could benefit from this targeted therapy.
Clinical • Companion diagnostic • EGFR exon 20
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR exon 20 insertion • MET mutation • EGFR exon 20 mutation
|
Guardant360® CDx • Oncomine™ Dx Target Test
|
Rybrevant (amivantamab-vmjw)
5ms
[VIRTUAL] Stacking on the Targets: Secondary Resistant, Potential Targetable Genetic Alterations in Patients With Epidermal Growth Factor Receptor NSCLC (IASLC-WCLC 2021)
One patient had BRAF V600E mutation and received BRAF+MEK inhibitors in addition to continuing osimertinib with excellent clinical response, and 1 had HER2 mutation who received carboplatin/pemetrexed/pembrolizumab. Ongoing trials such as the ORCHARD trial are looking at biomarker-driven therapies for patients who progress on osimertinib but do not account for rarer or newer actionable mutations. Real world data on specifics of resistance mutations to osimertinib could lay the foundation for more robust multi-arm clinical trials.
Clinical • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR1 (Fibroblast growth factor receptor 1)
|
BRAF V600E • EGFR mutation • BRAF V600 • EGFR L858R • EGFR T790M • MET amplification • EGFR exon 19 deletion • ALK fusion • RET mutation • ROS1 fusion • MET mutation • FGFR1 mutation • FGFR mutation • FGFR1 fusion • BRAF amplification
|
Keytruda (pembrolizumab) • Tagrisso (osimertinib) • carboplatin • pemetrexed
5ms
[VIRTUAL] Biomarker Testing for Advanced Lung Cancer by Next - Generation Sequencing in Elderly Patients. (IASLC-WCLC 2021)
Conclusion This is a relevant study for elderly population with stage IV NSCLC describing the mutational landscape of lung cancer patients on cancer biology and treatment outcome. Our study demonstrates the clinical utility of NGS testing for identifying actionable variants and treatment decision-making in advanced lung cancer in elderly population.
Clinical
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
KRAS G12C • MET amplification • ALK rearrangement • MET mutation • KRAS G12
|
FoundationOne® Liquid CDx • Oncomine Focus Assay
5ms
[VIRTUAL] Tepotinib Plus an EGFR TKI in Patients with EGFR - mutant NSCLC and Resistance to EGFR TKIs Due to MET Amplification (METamp) (IASLC-WCLC 2021)
Source Age* Gender Prior treatment Time on most recent prior EGFR TKI, months METamp,**GCN EGFR TKI*** Time on treatment,**** months Treatment ongoing**** INSIGHT PII 42 F Afatinib 5.7 13.9 Gefitinib 250 mg 53.1 Yes PII 66 M Erlotinib 9.8 13.3 Gefitinib 250 mg 50.3 Yes PII 68 F Erlotinib 15.8 6.7 Gefitinib 250 mg 48.3 Yes PII 52 F Gefitinib 26.8 12.4 Gefitinib 250 mg 22.1 No PII 53 F Gefitinib 46.3 7.7 Gefitinib 250 mg 21.1 No PII 67 M Gefitinib 6.6 5.2 Gefitinib 250 mg 14.2 No PIb 60 M Gefitinib, chemo, erlotinib 6.0 5.4 Gefitinib 250 mg 13.8 No PIb 63 M Gefitinib 11.5 7.3 Gefitinib 250 mg 13.1 No Clinical practice US 62 F Chemo, afatinib, osimertinib, immunotherapy 12.0 N/A (NGS] , Archer) Osimertinib 80 mg 6.7 Yes HK 79 M Gefitinib, osimertinib 11.5 10 (NGS; Foundation Medicine) Osimertinib 80 mg 6.3 Yes *At the beginning of combination treatment; **In the INSIGHT study, METamp was determined using FISH, in clinical practice one patient was tested by liquid biopsy using the Archer NGS assay, and one patient was tested by tissue biopsy using the Foundation Medicine NGS assay; ***EGFR TKI given in combination tepotinib 500mg (450 mg active moiety) treatment; ****As of March 2021. Tepotinib plus osimertinib is currently being investigated in the INSIGHT 2 study (NCT03940703) in patients with METamp EGFR-mutant NSCLC with acquired resistance to first-line osimertinib. Enrollment is ongoing in 125 sites in 17 countries; encouraging preliminary activity has been observed.
Clinical • IO biomarker
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET mutation
|
erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib • Tepmetko (tepotinib)
5ms
[VIRTUAL] Sequencing of PD - 1 Inhibitors and TKIs in Metastatic NSCLC with MET Exon 14 Skipping Mutation May Influence Survival (IASLC-WCLC 2021)
MET TKIs were received by 21 patients (17 crizotinib, 3 capmatinib, 1 cabozantinib), with an ORR of 29%...However, increased toxicity is seen when a TKI is used after ICI and careful monitoring is necessary. Future studies focusing on the optimal sequencing of TKIs and ICI-containing therapy should be prioritized, as well as broader access to newer generation MET TKIs with greater activity.
PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
PD-L1 expression • EGFR mutation • MET amplification • MET exon 14 mutation • MET mutation
|
Xalkori (crizotinib) • Cabometyx (cabozantinib tablet) • Tabrecta (capmatinib)
5ms
[VIRTUAL] The Characteristics of FGFR Genetic Aberrations in Chinese Lung Cancer Patients (IASLC-WCLC 2021)
Frequency of FGFR fusions Fusions Fusion region N (%) FGFR3-TACC3 EX18E:EX11 3(7.14%) EX17:EX8 3(7.14%) EX17:EX10 2(4.76%) EX18E:EX13 1(2.38%) EX8:EX9 1(2.38%) FGFR3-LETM1 EX8:Promoter 1(2.38%) FGFR3-SZT2 EX7:EX61 1(2.38%) FGFR3-PCDH7(intergenic) EX8:intergenic 1(2.38%) FAM53A(intergenic)-FGFR3 intergenic:EX18E,intergenic:EX8 2(4.76%) FGFR3-chr20 55284041 EX18E:chr20 55284041 1(2.38%) FGFR2-FAM184B EX17:EX8 1(2.38%) FGFR2-GRK5 EX17:EX1 1(2.38%) FGFR2-SORBS1 EX17:EX24 1(2.38%) FGFR2-PROM1 EX18:EX11 1(2.38%) FGFR2-chr10 122732846 EX17:chr10 122732846 1(2.38%) FGFR2-NPVF(intergenic) EX14:intergenic 1(2.38%) OPALIN-FGFR2 EX6E:EX2 1(2.38%) ATE1-FGFR2 EX11:EX2,EX5:EX17 2(4.76%) chr10 123156582-FGFR2 chr10 123156582:EX18 1(2.38%) DEC1(intergenic)-FGFR2 intergenic:EX6 1(2.38%) FGFR1-TACC1 EX1:EX2 1(2.38%) FGFR1-STAU1 EX1:EX7 1(2.38%) FGFR1-LETM2 EX12:EX8 1(2.38%) FGFR1-KCNU1(intergenic) EX3:intergenic 1(2.38%) FGFR1-SLC22A23 EX13:EX10 1(2.38%) FGFR1-ISL1(intergenic) EX8:intergenic,EX4:intergenic 2(4.76%) DDHD2-FGFR1 EX5:EX2 1(2.38%) ZMAT4-FGFR1 EX2:EX2 1(2.38%) HELZ-FGFR1 EX33E:EX6 1(2.38%) chr8 76149982-FGFR1 EX0:EX2 1(2.38%) chr8 138590655-FGFR1 EX0:EX2 1(2.38%) UNC5D(intergenic)-FGFR1 intergenic:EX2 1(2.38%) LOC100996508-FGFR1 EX1:EX2 1(2.38%) TACC1(intergenic)-FGFR1 intergenic:EX2 1(2.38%) Total 42(100%) Conclusion We report the prevalence of FGFR aberrations in a large lung cancer pts, including mutations, gene amplifications, gene deletion and one novel FGFR fusion. Our results revealed the potential therapeutic strategies with FGFR inhibitors for Chinese patients with lung cancer.
Clinical
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • FGFR (Fibroblast Growth Factor Receptor) • FGFR4 (Fibroblast growth factor receptor 4) • SORBS1 (Sorbin And SH3 Domain Containing 1)
|
MET amplification • FGFR1 amplification • EGFR overexpression • FGFR2 mutation • FGFR2 fusion • ALK fusion • RET mutation • ALK mutation • ROS1 fusion • MET mutation • FGFR mutation • FGFR2 overexpression • FGFR fusion • FGFR1 fusion • FGFR3 amplification • ALK-ROS1 fusion • FGFR2 expression
5ms
[VIRTUAL] EGFR - Mutant NSCLC With de novo or Acquired Squamous Histology: Molecular Features and Clinical Outcomes (IASLC-WCLC 2021)
Post-transformation, 3/10 were treated with third-generation EGFR TKIs (2 T790M+), yielding a median treatment duration of 3.4 months (range 1.4-11.6), 4/10 received taxane-based chemotherapy with a median treatment duration of 10.5 months (range 0.9-13.8), and 1/10 received pemetrexed-based chemotherapy with treatment duration of 2 months...(%) Carbo/taxol N/A N/A 4 (40) Carbo/pem N/A N/A 1 (10) 3rd-gen EGFR TKI N/A N/A 3 (30) MET inhibitor monotherapy N/A N/A 1 (10) Clinical Outcomes Duration of 1st Line Therapy, Median (Range) 8.1 mos (5.1-95.8) 6.2 mos (1.5-16.5) 11.1 mos (8.1-31.9) Overall Survival, Median (95% CI) 12.0 mos (9.9-NR) 14.3 mos (7.4-NR) 47.8 mos (11.1-50.6) Time to Squamous Transformation, Median (Range) N/A N/A 28.3 mos (8.5-70.7) Survival From Transformation, Median (95% CI) N/A N/A 13.5 mos (0-18.6) Conclusion Our findings confirm the rarity of squamous transformation in EGFR-mutant cancers and suggest that co-occurring genetic drivers of resistance may be common, in distinction from SCLC transformation. Further study is needed to investigate histologic transformation in acquired resistance. Chemotherapy tailored to squamous tumors may be beneficial, though prospective trials are needed.
Clinical • Clinical data
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • MET amplification • EGFR exon 19 deletion
|
paclitaxel • pemetrexed
5ms
[VIRTUAL] Profile of Next - Generation Sequencing (NGS) on MET exon 14 Skipping Mutation and MET Amplification in Lung Cancer: A Calibration Project in China (IASLC-WCLC 2021)
Our data indicate that the Chinese sequencing market and services are considerable and have a large room for advancement. Further data is needed to support standardization and clinical interpretation.
Next-generation sequencing
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation
5ms
[VIRTUAL] Spectrum of Resistance Mechanisms to First, Second and Third Generation Tyrosine Kinase Inhibitors in EGFR Mutant NSCLC Patients (IASLC-WCLC 2021)
Other mutations detected were CTNNB1 D32N, KRAS G12V, and PIK3CA E542K Conclusion Resistance development is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs. NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.
Clinical
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
|
TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • EGFR L858R • KRAS G12C • EGFR T790M • MET amplification • EGFR exon 19 deletion • EGFR amplification • PIK3CA H1047R • EGFR exon 20 insertion • KRAS G12V • EGFR C797S • EGFR exon 19 mutation • MET mutation • PIK3CA E542K • KRAS G13 • KRAS G12 • ALK translocation • EGFR T790M + exon 19 deletion • EGFR exon 20 mutation • BRAF G469A • EGFR exon 19 deletion + EGFR T790M • PIK3CA E542 • KRAS G13C • EGFR H835L • EGFR L833V • PIK3CA exon 9 mutation + HR positive • EGFR E709A • TP53 R213
|
Oncomine Focus Assay
5ms
[VIRTUAL] Tepotinib + Osimertinib for EGFR - Mutant NSCLC with Resistance to First - Line Osimertinib Due to MET amplification: INSIGHT 2 (IASLC-WCLC 2021)
In the INSIGHT study (NCT01982955), the combination of tepotinib and the EGFR TKI gefitinib (n=12) improved outcomes compared to chemotherapy (n=7) in patients with EGFR-mutant METamp NSCLC and EGFR TKI resistance (n=19). Approximately 125 sites in 17 countries are expected to participate in Europe: Belgium (3 sites), France (8), Germany (13), Italy (8), Netherlands (3), Russia (7) and Spain (11); Asia: China (19), Hong Kong (2), Japan (10), Korea (4), Malaysia (7), Singapore (3), Taiwan (6), Thailand (3) and Vietnam (4); and North America (US [14]). As of March 2021, 95 sites are active.
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification
|
Tagrisso (osimertinib) • gefitinib • Tepmetko (tepotinib)
5ms
[VIRTUAL] Clinical Characteristics of Patients With MET Amplification - Positive NSCLC After EGFR - TKI Therapy (IASLC-WCLC 2021)
Conclusion Our results demonstrated the distinct clinical characteristics of patients with MET amplification-positive NSCLC after EGFR-TKI therapy. Our clinical prediction can aid physicians in selecting patients eligible for MET amplification screening and therapeutic targeting.
Clinical
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR exon 19 deletion • EGFR exon 21 mutation
6ms
Frequency of actionable molecular drivers in lung cancer patients with precocious brain metastases. (PubMed, Clin Neurol Neurosurg)
No ALK, ROS1 or RET gene rearrangements were detected. Our findings suggest that patients with precocious BM of lung cancer harbor EGFR mutations, MET amplifications or FGFR1 amplifications as potential targeted treatment options.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1)
|
KRAS mutation • EGFR mutation • MET amplification • ALK rearrangement • FGFR1 amplification • RET rearrangement • MET mutation
6ms
A biparatopic antibody-drug conjugate to treat MET-expressing cancers, including those that are unresponsive to MET pathway blockade. (PubMed, Mol Cancer Ther)
In a cynomolgus monkey toxicology study, METxMET-M114 was well tolerated at a dose that provides circulating drug concentrations that are sufficient for maximal antitumor activity in mouse models. Our findings suggest that METxMET-M114, which takes advantage of the unique trafficking properties of our METxMET antibody, is a promising candidate for the treatment of MET-overexpressing tumors, with the potential to address some of the limitations faced by the MET function blockers currently in clinical use.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET overexpression • MET exon 14 mutation • MET expression • MET-H
6ms
Generation and Characterization of a New Preclinical Mouse Model of EGFR-Driven Lung Cancer with MET-Induced Osimertinib Resistance. (PubMed, Cancers (Basel))
Conversely, as also observed in patients, the crizotinib (anti-MET TKI) and osimertinib combination improved survival and reduced tumor burden in EGFR/MET mice, further validating the model's value for preclinical studies. We also found that in EGFR/MET mice, MET overexpression negatively regulated EGFR activity through MIG6 induction, a compensatory mechanism that allows the coexistence of the two onco-genic events. Our data suggest that single EGFR or MET inhibition might not be a good therapeutic option for EGFR-mutated lung cancer with MET amplification, and that inhibition of both pathways should be the best clinical choice in these patients.
Preclinical • Journal
|
EGFR (Epidermal growth factor receptor) • ERRFI1 (ERBB Receptor Feedback Inhibitor 1)
|
MET amplification • EGFR overexpression • MET overexpression • MET mutation
|
Xalkori (crizotinib) • Tagrisso (osimertinib)
6ms
Comparing GOZILA and COLOMATE: Ongoing Umbrella/Basket Trials Examining Genetic Testing in Gastrointestinal Malignancies. (PubMed, Oncology (Williston Park))
Both studies have identified patients eligible for studies by examining ERBB2 (HER2), BRAF V600E, BRAF non-V600E, and FGFR alterations, as well as MET amplification and rechallenge with anti-EGFR antibodies. The existence of various companion trials for common alterations that can be potential therapy targets on the 2 platforms can lead to future international collaboration.
Journal • Pan tumor
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR (Fibroblast Growth Factor Receptor)
|
BRAF V600E • MET amplification
6ms
[VIRTUAL] Tepotinib + osimertinib for EGFR-mutant NSCLC with resistance to first-line osimertinib due to MET amplification (METamp): INSIGHT 2 (ESMO 2021)
Tepotinib + gefitinib improved outcomes vs chemotherapy in pts with EGFR-mutant METamp NSCLC and EGFR TKI resistance (INSIGHT; NCT01982955). Recruitment is ongoing; approximately 125 sites in 17 countries are expected to participate. As of April 2021, 95 sites are active.
Clinical
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification
|
Tagrisso (osimertinib) • gefitinib • Tepmetko (tepotinib)
6ms
[VIRTUAL] Real-time clinical utility of ctDNA genomic alterations in untreated patients with advanced NSCLC (ESMO 2021)
Real-time ctDNA is feasible and clinically informative in unselected pts with newly diagnosed advanced NSCLC. Preliminary data showed that LB could support the treatment selection in 68% of pts. This study is still ongoing; final data and outcomes based on ctDNA will be presented at ESMO Congress.
Clinical • Circulating tumor DNA
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
BRAF V600E • HER-2 amplification • BRAF V600 • KRAS G12C • MET amplification • KRAS G12
|
InVisionFirst®-Lung
6ms
[VIRTUAL] Amivantamab monotherapy and in combination with lazertinib in post-osimertinib EGFR-mutant NSCLC: Analysis from the CHRYSALIS study (ESMO 2021)
Antitumor activity of ami + laz in the post-osi setting appears favorable even without molecular selection post osimertinib failure, supporting that simultaneous targeting of the extracellular and catalytic domains of EGFR provides additive benefits.
Combination therapy
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR C797S • MET mutation
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
6ms
Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma. (PubMed, Cancers (Basel))
EGFR/ERBB2/MET/KRAS amplifications, EGFR C797S, PIK3CA E545K, PTEN V9del, and CTNNB1 S45P were key resistance mechanisms identified by NGS. Serial assessment of ctDNA in plasma and saliva predicts response and resistance to osimertinib, with each assay having supplementary roles.
Journal • Circulating tumor DNA
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
|
EGFR mutation • HER-2 amplification • MET amplification • PIK3CA E545K • EGFR C797S • PIK3CA E545
|
Tagrisso (osimertinib)
6ms
The genomic characteristics of different progression patterns in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors. (PubMed, Ann Transl Med)
Mutations in RAD54L (P=0.018) and MYC (P=0.04) were more common in FP patients; HPD patients showed more frequent RAD54L mutations (P<0.001). We demonstrated different genomic characteristics across different progression patterns following ICI treatment, which might assist clinicians in the prediction of a patient's response, identifying candidates for more effective ICI therapy.
Clinical • Journal • Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • CDKN1B (Cyclin dependent kinase inhibitor 1B)
|
KRAS mutation • EGFR mutation • HER-2 amplification • MET amplification • HER-2 mutation • EGFR amplification • RET fusion • ALK fusion • ALK mutation • MET mutation • ATRX mutation • ALK amplification • RAD54L mutation • NTRK1 mutation
6ms
Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma. (PubMed, Clin Cancer Res)
RCC harbors a low prevalence of clinically actionable alterations compared to other tumors and the evidence supporting their clinical use is limited. These aberrations were found to be more common in advanced disease and seem to occur later during tumor evolution. Our study provides new insights on the role of targeted therapies for RCC and highlights the need for additional research to improve treatment selection using genomic profiling.
Journal • Tumor Mutational Burden
|
TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability)
|
MET amplification
|
MSK-IMPACT
6ms
Landscape of Biomarkers in Non-small Cell Lung Cancer Using Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry. (PubMed, Pathol Oncol Res)
In addition, in the PD-L1 disease subset, BRAF mutations, MET mutations, MET amplifications, and KRAS mutations were significantly enriched; and in the PD-L1, EGFR mutations, ERBB2 mutations, STK11 mutations, and KEAP1 mutations were enriched. These findings highlight the improved clinical utility of combining CGP with IHC to expand the biomarker-guided therapeutic options available for patients with NSCLC, relative to single biomarker testing alone.
Journal • Tumor Mutational Burden • IO Companion diagnostic • PD(L)-1 Biomarker • IO biomarker • PD(L)-1 companion diagnostic
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
|
PD-L1 expression • KRAS mutation • EGFR mutation • BRAF mutation • MET amplification • STK11 mutation • KEAP1 mutation • MET mutation
6ms
Prognosis and Concurrent Genomic Alterations in Patients With Advanced NSCLC Harboring MET Amplification or MET Exon 14 Skipping Mutation Treated With MET Inhibitor: A Retrospective Study. (PubMed, Front Oncol)
Concurrent mutations may deteriorate the PFS of MET TKIs in NSCLC patients with MET amplification or METex14 skipping mutations. PIK3CA mutations may confer primary resistance to MET TKIs in patients with MET amplification.
Retrospective data • Journal
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
PIK3CA mutation • MET amplification • MET exon 14 mutation • MET mutation
6ms
Acquired resistance to third-generation EGFR tyrosine kinase inhibitors in patients with de novo EGFR-mutant non-small cell lung cancer. (PubMed, J Thorac Oncol)
Activation of bypass pathways and the EGFR or EGFR mutation were identified as acquired resistance mechanisms to third-generation EGFR TKIs in NSCLC patients with de novo EGFR mutation. In addition, MTOR- and EGFR-mutant NSCLC cells were sensitive to osimertinib plus mTOR inhibitors.
Clinical • Preclinical • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET mutation • EGFR H1975
|
Tagrisso (osimertinib)
6ms
CoC: A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLC (clinicaltrials.gov)
P2, N=56, Recruiting, AstraZeneca | Trial completion date: May 2023 --> Feb 2024 | Trial primary completion date: May 2022 --> Feb 2023
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
6ms
Acquired Resistance to KRAS Inhibition in Cancer. (PubMed, N Engl J Med)
Diverse genomic and histologic mechanisms impart resistance to covalent KRAS inhibitors, and new therapeutic strategies are required to delay and overcome this drug resistance in patients with cancer. (Funded by Mirati Therapeutics and others; ClinicalTrials.gov number, NCT03785249.).
Preclinical • Journal
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1)
|
KRAS mutation • BRAF mutation • NRAS mutation • MET amplification • PTEN mutation • KRAS G12D • ALK fusion • NF1 mutation • RET mutation • KRAS G13 • KRAS G12 • NRAS G12D • NRAS G13 • NRAS Q61 • FGFR3 fusion • KRAS Q61H • BRAF amplification
|
Lumakras (sotorasib) • adagrasib (MRTX849)
6ms
MET inhibition downregulates DR4 expression in MET-amplified lung cancer cells with acquired resistance to EGFR inhibitors through suppressing AP-1-mediated transcription. (PubMed, Neoplasia)
Osimertinib combined with MET inhibition synergistically induces apoptosis in the MET-amplified EGFR mutant NSCLC cells accompanied with augmented DR4 reduction both in vitro and in vivo. Furthermore, MET inhibition combined with TRAIL enhanced killing of MET-amplified EGFR mutant HCC827/AR cells, but not HCC827 parental cells. These data collectively suggest that DR4 may possess an unrecognized anti-apoptotic function, contributing to apoptosis resistance under given conditions.
Preclinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • MET amplification • EGFR expression • AR mutation • MET expression • EGFR mutation + MET amplification
|
Tagrisso (osimertinib)
6ms
Integrated Analysis of Genomic and Immunological Features in Lung Adenocarcinoma With Micropapillary Component. (PubMed, Front Oncol)
We identified multiple novel MPC-enriched genetic changes that could help us understand the nature of this aggressive cancer subtype. High MPC tumors tended to have elevated levels of TMBs, T cell infiltration, and immunosuppression than low MPC tumors, implying the potential link between MPC content and sensitivity to immunotherapy.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • CD8 (cluster of differentiation 8) • NKX2-1 (NK2 Homeobox 1) • CD4 (CD4 Molecule)
|
PD-L1 expression • MET amplification • MTOR mutation • mTOR amplification
6ms
Co-Occurring Potentially Actionable Oncogenic Drivers in Non-Small Cell Lung Cancer. (PubMed, Front Oncol)
Approximately 1.5% of NSCLCs harbored co-occurring potentially actionable oncogenic drivers, commonly involving EGFR mutations. Co-occurring actionable targets may impact the efficacy of TKIs; therefore, future clinical trials in these patients should be anticipated to tailor the combination or sequential treatment strategies.
Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 amplification • MET amplification
6ms
ADVL1622: Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors (clinicaltrials.gov)
P2, N=109, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jun 2022 --> Jun 2021
Clinical • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • AXL (AXL Receptor Tyrosine Kinase)
|
MET amplification • MET overexpression • RET mutation • RET rearrangement • MET mutation • AXL overexpression
|
Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
7ms
The NHance Mutation-Equipped Anti-MET Antibody ARGX-111 Displays Increased Tissue Penetration and Anti-Tumor Activity in Advanced Cancer Patients. (PubMed, Biomedicines)
When escalated to 1 mg/kg, a partial response was reached. Furthermore, decreased numbers of CTC (75%) possibly by the enhanced tumor cell killing witnessed the modes of action of the drug, warranting further clinical investigation of ARGX-111.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET mutation
|
ARGX-111
7ms
Distinct Characteristics and Clinical Outcomes to Predict the Emergence of MET Amplification in Patients with Non-Small Cell Lung Cancer Who Developed Resistance after Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. (PubMed, Cancers (Basel))
Our results demonstrated the distinct clinical characteristics of patients with MET amplification-positive NSCLC after EGFR-TKI therapy. Our clinical prediction can aid physicians in selecting patients eligible for MET amplification screening and therapeutic targeting.
Clinical • Clinical data • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion
7ms
Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds. (PubMed, BMC Pulm Med)
Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics.
Preclinical • Journal
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
|
KRAS mutation • EGFR mutation • PIK3CA mutation • MET amplification • MAP2K1 mutation • KRAS amplification • EGFR H1975 • PIK3CA mutation + KRAS mutation
|
Gilotrif (afatinib) • Mektovi (binimetinib) • buparlisib (BKM120) • tivantinib (ARQ 197)
7ms
ADVL1622: Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors (clinicaltrials.gov)
P2, N=146, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jun 2022
Clinical • Trial completion date • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • AXL (AXL Receptor Tyrosine Kinase)
|
MET amplification • MET overexpression • RET mutation • RET rearrangement • MET mutation • AXL overexpression
|
Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
7ms
Volitinib in Treating Patients With Recurrent or Refractory Primary CNS Tumors (clinicaltrials.gov)
P1, N=50, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting
Clinical • Enrollment open
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET mutation • MET fusion • HGF amplification
|
Orpathys (savolitinib)
7ms
Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours. (PubMed, BMJ Open)
After the patients treated with vemurafenib, niraparib and palbociclib acquire resistance, they will receive combination treatment with sintilimab or atezolizumab. The results from this study will be actively disseminated through manuscript publications and conference presentations. NCT04423185; ChiCTR2000039310.
Clinical • P2 data • Journal • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin-dependent kinase inhibitor 2A)
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BRCA2 mutation • BRCA1 mutation • EGFR mutation • HER-2 amplification • HER-2 overexpression • BRAF mutation • MET amplification • KIT mutation • ALK fusion • CDKN2A mutation • ROS1 fusion • MET mutation • BRAF amplification
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Zelboraf (vemurafenib) • Ibrance (palbociclib) • Tecentriq (atezolizumab) • Zejula (niraparib) • Tyvyt (sintilimab)
7ms
Co-occurring MET Amplification Predicts Inferior Clinical Response to First-Line Erlotinib in Advanced Stage EGFR-Mutated NSCLC Patients. (PubMed, Clin Lung Cancer)
Co-occurring MET amplification in pretreatment ctDNA samples predict inferior clinical response to first-line erlotinib in advanced-stage, EGFR-mutated NSCLC patients. Co-occurring oncogenic alterations were associated with inferior response and may be potential predictors of clinical outcome.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • MET amplification
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erlotinib
7ms
Clinical • New P2 trial
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation • MET mutation
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Tabrecta (capmatinib)
7ms
Clinical • New P2 trial
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification
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Orpathys (savolitinib)
7ms
Cabozantinib S-malate in Treating Patients With Metastatic Pheochromocytomas or Paragangliomas That Cannot Be Removed by Surgery (clinicaltrials.gov)
P2, N=22, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2020 --> Dec 2023 | Trial primary completion date: Dec 2020 --> Dec 2022
Clinical • Trial completion date • Trial primary completion date
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MET (MET proto-oncogene, receptor tyrosine kinase) • IL6 (Interleukin 6) • CHGA (Chromogranin A) • CRP (C-reactive protein)
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MET amplification • MET expression
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Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
7ms
MET amplification attenuates lung tumor response to immunotherapy by inhibiting STING. (PubMed, Cancer Discov)
Mechanistically, we found that oncogenic MET signaling induces phosphorylation of UPF1 and downregulates tumor cell STING expression via modulation of the 3'-UTR length of STING by UPF1. Decreased efficiency of ICB by MET amplification can be overcome by inhibiting MET.
Journal • IO biomarker
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MET (MET proto-oncogene, receptor tyrosine kinase) • CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1) • XIST (X Inactive Specific Transcript)
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MET amplification
7ms
[VIRTUAL] Clinical Molecular Profiling of IDH-wildtype Glioblastoma Adult Patients: Old Patterns and New Insights (AANP 2021)
Presence of MGMTp methylation was similar between TERTpMUT and TERTpWT groups (34% versus 29%, p-value 0.38). Clinical molecular profiling of IDHWT-GBM recapitulates and expands the spectrum of previously reported patterns, underscoring the molecular heterogeneity of IDHWT-GBM and providing a valuable dataset to unravel novel patterns and associations.
Clinical
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
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TP53 mutation • EGFR mutation • BRAF mutation • MET amplification • PTEN mutation • CDKN2A deletion • NF1 mutation • MET mutation • ATRX mutation • PDGFRA mutation • MET fusion • PPM1D mutation • TERT mutation
7ms
Beyond Conventional: The New Horizon of Targeted Therapy for the Treatment of Advanced Non Small Cell Lung Cancer. (PubMed, Front Oncol)
Therefore, genetic testing, including at least EGFR mutations and ALK/ROS1 rearrangements, should be performed in all NSCLC patients (in particular with adenocarcinoma) who received a diagnosis of advanced disease. This review focuses on novel druggable oncogenic drivers, such as MET exon 14 mutations/MET amplification, RET fusions, BRAF V600E mutations, KRAS G12C mutations, NTRK rearrangements, and HER2 alterations.
Review • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • KRAS G12C • MET amplification • RET fusion • ALK rearrangement • MET exon 14 mutation • RET mutation • ROS1 rearrangement • MET mutation • KRAS G12 • BRAF amplification
8ms
[VIRTUAL] Optimal Therapeutic Approaches for Patients with Genomic Aberrations beyond EGFR, ALK and ROS1 (ASCO 2021)
Design, eligibility criteria and key findings from the Phase II VISION trial leading to the recent FDA approval of tepotinib for patients with metastatic NSCLC harboring MET exon 14 skipping alterations Rationale for the design of the ongoing Phase II NAUTIKA1 neoadjuvant and adjuvant study of alectinib, entrectinib, vemurafenib/cobimetinib or pralsetinib for patients with resectable Stage II-III NSCLC harboring ALK, ROS1, NTRK, BRAF V600 or RET molecular alterations Key efficacy and safety outcomes from the Phase II GEOMETRY mono-1 trial supporting the FDA approval of capmatinib for patients with MET exon 14 mutation-positive metastatic NSCLC Practical integration and optimal sequencing of capmatinib and tepotinib into current clinical management of patients with advanced NSCLC harboring MET exon 14 skipping alterations Available safety and efficacy results from the LIBRETTO-001 and ARROW trials leading to the FDA approvals of selpercatinib and pralsetinib for patients with RET fusion-driven NSCLC; optimal integration into clinical practice Design, eligibility and key endpoints of the Phase III LIBRETTO-431 and AcceleRET Lung studies assessing selpercatinib and pralsetinib, respectively, compared to first-line chemotherapy with or without pembrolizumab in patients with treatment-naïve RET fusion-positive advanced NSCLC Frequency and clinical impact of HER2 overexpression or mutations in NSCLC; key efficacy and safety findings from the Phase II DESTINY-Lung01 study evaluating trastuzumab deruxtecan in HER2-overexpressing or mutated NSCLC FDA breakthrough therapy designation and potential nonprotocol role of trastuzumab deruxtecan in patients with HER2-positive metastatic NSCLC Clinical impact of HER3 upregulation as a mechanism of resistance to EGFR tyrosine kinase inhibitors; early efficacy and safety findings with patritumab deruxtecan in a Phase I trial for previously treated patients with EGFR mutation-positive unresectable or metastatic NSCLC Ongoing Phase II HERTHENA-Lung01 trial of patritumab deruxtecan for patients with locally advanced or metastatic EGFR mutation-positive NSCLC who have received prior treatment with osimertinib and at least 1 platinum-based chemotherapy regimen Design, eligibility criteria and key endpoints of the ongoing Phase III GEOMETRY-E trial of capmatinib in combination with osimertinib versus chemotherapy as second-line therapy for patients with locally advanced or metastatic NSCLC harboring non-T790M EGFR activating mutations as well as MET amplification after disease progression on a first/second EGFR tyrosine kinase inhibitor or osimertinib Mechanism of action of sotorasib and available efficacy and safety data from the Phase II CodeBreak 100 trial evaluating sotorasib in patients with previously treated KRAS G12C mutation-positive NSCLC; FDA priority review for sotorasib for KRAS G12C-mutated advanced NSCLC Other ongoing and planned clinical trials investigating novel agents and strategies for patients with advanced NSCLC harboring targetable gene alterations (eg, ECOG-ACRIN LUNG-MAP)
Clinical • PD(L)-1 Biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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HER-2 positive • KRAS mutation • EGFR mutation • HER-2 overexpression • BRAF V600 • KRAS G12C • EGFR T790M • MET amplification • RET fusion • MET exon 14 mutation • MET mutation • KRAS G12 • RET positive
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Keytruda (pembrolizumab) • Tagrisso (osimertinib) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Cotellic (cobimetinib) • Alecensa (alectinib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Lumakras (sotorasib) • Retevmo (selpercatinib) • Gavreto (pralsetinib) • patritumab deruxtecan (U3-1402) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
8ms
[VIRTUAL] PERSPECTIVE: Tepotinib plus cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer and acquired resistance to anti-EGFR antibody therapy due to MET amplification (ESMO-GI 2021)
Tepotinib plus gefitinib has shown improved outcomes in patients with EGFR-mutant METamp NSCLC and acquired EGFR TKI resistance versus chemotherapy (INSIGHT: NCT01982955). In these patients, progression-free survival (PFS) was 16.6 vs 4.2 months (HR=0.13; 90% CI: 0.04, 0.43) and overall survival (OS) was 37.3 vs 13.1 months (HR=0.08; 90% CI: 0.01, 0.51). In patients with mCRC and acquired resistance to anti-EGFR antibody therapy due to METamp, tepotinib plus anti-EGFR antibody cetuximab may be active and provide an effective therapeutic option.
Clinical • Preclinical
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BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation
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Erbitux (cetuximab) • gefitinib • Tepmetko (tepotinib)
8ms
A Clinical Study Preliminary Efficacy of LM-061 Tablet in Subjects With Advanced Tumours (clinicaltrials.gov)
P1/2, N=87, Recruiting, LaNova Medicines Limited | Not yet recruiting --> Recruiting
Clinical • Enrollment open
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation • MET mutation • MET expression
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LM-061
8ms
Molecular characterization of ctDNA from Chinese patients with advanced gastric adenocarcinoma reveals actionable alterations for targeted and immune therapy. (PubMed, J Mol Med (Berl))
Potentially actionable genomic alterations were identified in 45.5% of patients, suggesting clinical utility for ctDNA NGS in advance stage GACs. There was evidence of clinical benefit in one GAC patient with MET amplification treated with MET inhibitor.
Clinical • Journal • Tumor Mutational Burden • Circulating tumor DNA
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • LRP1B (LDL Receptor Related Protein 1B)
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TMB-H • MET amplification
8ms
Resistance Profile of Osimertinib in Pre-treated Patients With EGFR T790M-Mutated Non-small Cell Lung Cancer. (PubMed, Front Oncol)
Histological transformation into small cell carcinoma occurred in one patient. This real-world life study highlights the relevance of re-biopsy at the time of disease progression, contributing to understand resistance mechanisms and to guide treatment strategies.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • DCTN1 (Dynactin Subunit 1)
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EGFR mutation • PIK3CA mutation • EGFR T790M • MET amplification • ALK fusion • EGFR C797S • MET mutation • CTNNB1 mutation • DCTN1-ALK fusion
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Tagrisso (osimertinib)
8ms
Efficacy and Safety of Combination Treatment With Apatinib and Osimertinib After Osimertinib Resistance in Epidermal Growth Factor Receptor-Mutant Non-small Cell Lung Carcinoma-A Retrospective Analysis of a Multicenter Clinical Study. (PubMed, Front Mol Biosci)
The most common adverse events were hypertension (30.7%, 12/39), diarrhea (15.4%, 6/39), and proteinuria (12.8%, 5/39). The combination of apatinib and osimertinib improved the ORR and the DCR of patients with osimertinib-refractory EGFR-positive NSCLC, thus making it a reasonable treatment choice after the development of osimertinib resistance.
Retrospective data • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • TYK2 (Tyrosine Kinase 2)
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TP53 mutation • EGFR mutation • HER-2 amplification • PIK3CA mutation • MET amplification • HER-2 mutation
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Tagrisso (osimertinib) • AiTan (rivoceranib)
8ms
HIF-1 Inhibitor YC-1 Reverses the Acquired Resistance of EGFR-Mutant HCC827 Cell Line with MET Amplification to Gefitinib. (PubMed, Oxid Med Cell Longev)
p-Met level was correlated with HIF-1α level, while there was no correlation between p-Met level and p-EGFR level. HIF-1 inhibitor YC-1 is able to reverse the acquired resistance of HCC827 GR to gefitinib, and the regulation of the HIF-1 pathway on MET may be one of the mechanisms.
Preclinical • Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • HIF1A (Hypoxia inducible factor 1, alpha subunit)
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EGFR mutation • MET amplification • MET mutation
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gefitinib
8ms
CHRYSALIS: Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1, N=460, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Mar 2021 --> Jan 2024
Clinical • Trial primary completion date
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MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR exon 20 insertion • MET exon 14 mutation • EGFR C797S • MET mutation • EGFR exon 20 mutation
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carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
8ms
Clinical • New P1/2 trial
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation • MET mutation • MET expression
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LM-061
8ms
TP53 mutation and MET amplification in circulating tumor DNA analysis predict disease progression in patients with advanced gastric cancer. (PubMed, PeerJ)
Simultaneously, Kaplan-Meier analysis showed that patients with MET amplification also had shorter OS than these with MET without amplification (P < 0.001). TP53 and MET are the two common frequently mutant genes in ctDNA of AGC patients.TP53 mutation and MET amplification in ctDNA could predict disease progression of AGC patients.
Clinical • Journal • Circulating tumor DNA
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)
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TP53 mutation • EGFR mutation • MET amplification • MET mutation
9ms
Comprehensive Molecular Characterization of Chinese Patients with Glioma by Extensive Next-Generation Sequencing Panel Analysis. (PubMed, Cancer Manag Res)
Our multigene NGS in the simultaneous evaluation of multiple relevant markers revealed several novel genetic alterations in Chinese patients with glioma. NGS-based molecular analysis is a reliable and effective method for diagnosing brain tumors, assisting clinicians in evaluating additional potential therapeutic options, such as targeted therapy, for glioma patients in different racial/ethnic groups.
Clinical • Journal • Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • H3F3A (H3 Histone Family Member 3A)
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TP53 mutation • EGFR mutation • MET amplification • PTEN mutation • CDKN2A mutation • MET mutation • TERT mutation
9ms
MET alterations and their impact on the future of non-small cell lung cancer (NSCLC) targeted therapies. (PubMed, Expert Opin Ther Targets)
We offer our perspective and examine new information on the mechanisms of the MET alterations in this review.Expert OpinionGiven the trends currently involving the targeting of MET altered malignancies, there will most likely be a continued rapid expansion of testing, novel tyrosine kinase inhibitors and potent antibody approaches. Combinations treatments will be necessary to optimize management of advanced and early disease.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation • MET mutation • MET fusion
9ms
[VIRTUAL] Genetic landscape of melanoma in China reveals enrichment of fusions in driver-negative melanoma. (ASCO 2021)
As was reported, AGAP3-BRAF fusion was the mechanism by which melanoma patients with BRAF V600E mutations developed resistance to vemurafenib; GTF2I-BRAF fusion mediated the activation of MAPK pathway in fibrous astrocytoma... Through DNA-based NGS, the mutation landscape of Chinese melanoma patients was depicted . BRAF was the most frequently mutated driver gene with the main mutation type of V600E (19.7%) which was significantly lower than that of white race in TCGA-SKCM database (44.2%) . On the other hand, DNA-based NGS can detect potentially druggable fusions, and compared with driver positive melanoma patients, fusions were enriched in patients with no driver mutations detected .
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • GNAQ (G Protein Subunit Alpha Q) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • GNA11 (G Protein Subunit Alpha 11) • CDK4 (Cyclin-dependent kinase 4) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4) • TPM3 (Tropomyosin 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • DCTN1 (Dynactin Subunit 1)
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BRAF V600E • KRAS mutation • HER-2 amplification • NRAS mutation • BRAF V600 • MET amplification • HRAS mutation • MYC amplification • ALK fusion • NF1 mutation • CCND1 amplification • NRAS Q61R • BRAF fusion • NRAS Q61 • HRAS Q61R
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Onco PanScan™
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Zelboraf (vemurafenib)
9ms
[VIRTUAL] Role of capmatinib in MET exon 14-mutated advanced non-small cell lung cancer (NSCLC): A systematic review. (ASCO 2021)
Our results showed that capmatinib has promising anti-tumor activity in patients with NSCLC harboring MET exon 14 skipping mutation . The efficacy and tolerability profile of capmatinib is remarkable, particularly in treatment-naïve patients . Although the GEOMETRY Mono-1 trial is still ongoing, further clinical studies with long-term follow-up are needed.
Review • IO biomarker
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation • MET mutation
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Tabrecta (capmatinib)
9ms
[VIRTUAL] KEAP1 mutations in squamous cell lung cancer. (ASCO 2021)
KEAP1 mutations occur commonly in SqCC patients and do not impact the efficacy of ICI in terms of OS . To identify prognostic markers for response to ICI further research is needed.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • KEAP1 (Kelch Like ECH Associated Protein 1)
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PD-L1 expression • TP53 mutation • KRAS mutation • MET amplification • PTEN mutation • FGFR1 amplification • KEAP1 mutation • FGFR1 expression
9ms
[VIRTUAL] Primary and secondary resistance mechanisms in first, second and third generation tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer patients. (ASCO 2021)
Primary and secondary acquired resistance is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs . NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.
Clinical
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • EGFR L858R • KRAS G12C • EGFR T790M • MET amplification • EGFR exon 19 deletion • EGFR amplification • PIK3CA H1047R • EGFR exon 20 insertion • KRAS G12V • EGFR C797S • EGFR exon 19 mutation • MET mutation • PIK3CA E542K • KRAS G13 • KRAS G12 • ALK translocation • EGFR T790M + exon 19 deletion • EGFR exon 20 mutation • BRAF G469A • EGFR exon 19 deletion + EGFR T790M • PIK3CA E542 • KRAS G13C • PIK3CA exon 9 mutation + HR positive • EGFR E709A • TP53 R213
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Oncomine Focus Assay
9ms
[VIRTUAL] Clinical significance of next-generation sequencing in Chinese patients with relapsed/refractory Wilm’s tumor. (ASCO 2021)
We discovered some driver genes mutations which potentially sensitive to the corresponding targeted drugs in Chinese R/R WT patients . Large sample size was needed to provide a better understanding of molecular features in R/R WT patients to achieve precision medicine.
Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker • Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • FGFR1 (Fibroblast growth factor receptor 1) • NF1 (Neurofibromin 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MDM4 (The mouse double minute 4) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • AMER1 (APC Membrane Recruitment Protein 1)
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PD-L1 expression • EGFR mutation • HER-2 amplification • MET amplification • FGFR1 amplification • PD-L1 negative • CHEK2 mutation • FANCA mutation • HER-2 amplification + PD-L1 expression
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VENTANA PD-L1 (SP263) Assay
9ms
[VIRTUAL] Sequencing of systemic therapies in advanced NSCLC with MET exon 14 skipping mutation: A multicenter experience. (ASCO 2021)
MET TKIs were received by 18 patients (16 crizotinib, 1 capmatinib, 1 cabozantinib), with an ORR of 28% (30% amongst those who received crizotinib first line)... Patients with MET ex14 NSCLC benefit from ICI irrespective of PD-L1 expression and smoking history . ORR and PFS with earlier generation TKIs (crizotinib) were poor . Increased toxicity is seen when a TKI is used after ICI and careful monitoring is necessary .
Clinical • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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PD-L1 expression • EGFR mutation • MET amplification • MET exon 14 mutation • MET mutation
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Xalkori (crizotinib) • Cabometyx (cabozantinib tablet) • Tabrecta (capmatinib)
9ms
[VIRTUAL] Evaluation of somatic and germline mutations in Chinese patients with gallbladder carcinoma reveals clinically actionable targets. (ASCO 2021)
Importantly, 9% (10/118) patients carried activating PIK3CA mutations including P104L, E110del, E545K/Q/G, E542K, E726K and T1025S which may be targeted by PIK3CA inhibitor alpelisib... Our results indicated that activating mutations in the ErbB and PI3K signaling pathways are the major driving events of GBC . The results of genomic profiling can guide physicians to enroll a significant portion of GBC patients into genomically matched clinical trials.
Clinical • PARP Biomarker • BRCA Biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • KMT2C (Lysine Methyltransferase 2C) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • ARID2 (AT-Rich Interaction Domain 2) • ELF3 (E74 Like ETS Transcription Factor 3)
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TP53 mutation • BRCA1 mutation • EGFR mutation • PIK3CA mutation • MET amplification • ATM mutation • PTEN mutation • STK11 mutation • PIK3CA E545K • ARID1A mutation • PALB2 mutation • NF1 mutation • PIK3CA E542K • HER-2 S310F • ERBB3 mutation • PIK3CA E545 • PIK3CA E542
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Onco PanScan™
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Piqray (alpelisib)
9ms
[VIRTUAL] Profiling genomic characteristics related to immunotherapy for gastric cancer with amplified MET. (ASCO 2021)
Genomic characteristics of GCA with amplified MET are associated with adverse response to immunotherapy and thus it should be carefully evaluated when these patients are treated with immunotherapy.
Tumor Mutational Burden • BRCA Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • CCND1 (Cyclin D1) • PALB2 (Partner and localizer of BRCA2) • PBRM1 (Polybromo 1) • FGF19 (Fibroblast growth factor 19) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • ERCC2 (Excision repair cross-complementation group 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MSH2 (MutS Homolog 2) • FGF3 (Fibroblast growth factor 3) • JAK1 (Janus Kinase 1) • PMS2 (PMS1 protein homolog 2) • B2M (Beta-2-microglobulin) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • FGF4 (Fibroblast growth factor 4) • RNF43 (Ring Finger Protein 43) • CDK6 (Cyclin-dependent kinase 6) • RAD50 (RAD50 Double Strand Break Repair Protein) • AXIN1 (Axin 1)
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KRAS mutation • BRCA1 mutation • EGFR mutation • MET amplification • ATM mutation • PTEN mutation • STK11 mutation • DNMT3A mutation • PALB2 mutation • TMB-L • PBRM1 mutation • CCND1 amplification • CTNNB1 mutation • CHEK2 mutation • RNF43 mutation • FANCA mutation • RAD50 mutation • PMS2 mutation
9ms
[VIRTUAL] PERSPECTIVE: Tepotinib + cetuximab in patients (pts) with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC) and acquired resistance to anti-EGFR antibody therapy due to MET amplification (METamp). (ASCO 2021)
Tepotinib + gefitinib demonstrated improved outcomes in pts with EGFR-mutant METamp NSCLC and acquired EGFR TKI resistance vs chemotherapy (INSIGHT: NCT01982955) . Retrospective assessment of best overall response, DoR and PFS by an independent review committee may be conducted . No formal statistical hypothesis will be tested in this exploratory study.
Preclinical • Clinical
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BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation
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Erbitux (cetuximab) • gefitinib • Tepmetko (tepotinib)
9ms
[VIRTUAL] Genomic profiling of KRAS wide-type pancreatic ductal adenocarcinomas identifies targetable genetic alterations. (ASCO 2021)
We found one classic EGFR activing mutation (L747_A750delinsP) and one MAP2K1 activating mutation (F53_Q58delinsL), which can be targeted by EGFR-TKIs and MEK inhibitor trametinib, respectively...We also found STK11/TSC2 inactivating mutations and a dominant-negative mutation of PTEN (R130Q) which could be targeted by mTOR inhibitor everolimus and AKT inhibitor capivasertib, respectively... The mutational landscape of our PDAC cohort provided compelling evidence that targetable driver mutations accounted for a significant portion of KRAS wide-type tumors . Our findings demonstrated that genomic profiling of PDAC patients can enable physicians to optimize their clinical management and enroll them into genomically matched clinical trials.
PARP Biomarker • BRCA Biomarker
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PALB2 (Partner and localizer of BRCA2) • TSC2 (TSC complex subunit 2) • NCOA4 (Nuclear Receptor Coactivator 4) • ELF3 (E74 Like ETS Transcription Factor 3)
|
BRAF V600E • KRAS mutation • BRCA1 mutation • EGFR mutation • BRAF V600 • MET amplification • PTEN mutation • RET fusion • STK11 mutation • PALB2 mutation • BRAF fusion • TSC2 mutation • ERBB3 mutation • NCOA4-RET fusion • EGFR L747_A750delinsP
|
Onco PanScan™
|
Mekinist (trametinib) • everolimus • capivasertib (AZD5363)
9ms
[VIRTUAL] Amivantamab in combination with lazertinib for the treatment of osimertinib-relapsed, chemotherapy-naïve EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC) and potential biomarkers for response. (ASCO 2021)
Treatment with the combination of amivantamab and lazertinib yielded responses in 36% of chemotherapy-naïve pts who progressed on osi . Among these pts, genetic EGFR and MET-based biomarkers of resistance identified a subgroup of pts more likely to respond to amivantamab and lazertinib, although additional pts lacking identified resistance markers also responded . An IHC-based approach may identify pts most likely to benefit from the combination regimen, but further investigation is warranted.
Combination therapy
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR expression • MET mutation • MET expression
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
9ms
[VIRTUAL] Subcutaneous delivery of amivantamab in patients with advanced solid malignancies: PALOMA, an open-label, multicenter, dose escalation phase 1b study. (ASCO 2021)
To mitigate infusion related reactions (IRR), medication with steroid, paracetamol, and antihistamine will be given pre-infusion and as clinically indicated post-infusion . Blood samples will be collected to assess PK, pharmacodynamics, and immunogenicity . A Study Evaluation Team composed of investigators and sponsor representatives will review safety and PK data to make decisions about dose escalation and cohort expansion throughout the conduct of the study.
P1 data • Clinical
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET mutation
|
Rybrevant (amivantamab-vmjw) • amivantamab SC (Ami-LC) • paracetamol
9ms
[VIRTUAL] Capmatinib in MET exon 14-mutated, advanced NSCLC: Updated results from the GEOMETRY mono-1 study. (ASCO 2021)
Results of Cohort 7 confirm those previously reported for Cohort 5b showing higher efficacy of capmatinib when used as 1L in METex14 NSCLC pts . A clinically meaningful median OS of 20.8 mo in 1L (Cohort 5b) and of 13.6 mo in relapse (Cohort 4) was also observed and, together with the continued manageable toxicity profile, the data support capmatinib as a valuable targeted treatment option for METex14 NSCLC pts.
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation
|
FoundationOne® CDx
|
Tabrecta (capmatinib)
9ms
[VIRTUAL] Phase 1b/2 study of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated non-small cell lung cancer who received prior therapy: Final overall survival and safety. (ASCO 2021)
Capmatinib 400 mg bid in combination with gefitinib 250 mg qd was well-tolerated and showed encouraging clinical activity in patients with EGFR-mutant and MET-dysregulated NSCLC.
Clinical • P1/2 data
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • MET mutation • MET-H
|
gefitinib • Tabrecta (capmatinib)
9ms
[VIRTUAL] A large real-world study on the effectiveness of the combined inhibition of EGFR and MET in EGFR-mutant advanced non-small cell lung cancer (NSCLC). (ASCO 2021)
Our study provides real-world clinical evidence, in the largest cohort to date, that simultaneous inhibition of EGFR and MET improves clinical outcomes of patients with EGFR-mutant NSCLC who acquired MET amplification from prior EGFR-TKI therapy, indicating that combinatorial regimen of EGFR-TKI and MET-TKI could be a more effective therapeutic strategy in this subset of patients.
Clinical • Real-world evidence
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDK4 (Cyclin-dependent kinase 4)
|
TP53 mutation • BRAF V600E • EGFR mutation • HER-2 amplification • BRAF V600 • EGFR T790M • MET amplification • EGFR amplification • MET mutation • KRAS amplification • NRAS Q61 • KRAS Q61H • EGFR L718Q • MET D1228H
|
Xalkori (crizotinib)
9ms
[VIRTUAL] The value of defining molecular resistance in patients with progressive EGFR and ALK-driven lung cancer in a public system. (ASCO 2021)
The majority, 81% (n = 22) had EGFR mutated NSCLC, and had progressed on EGFR TKIs (15 with previously identified T790M had progressed on osimertinib), and 19% (n = 5) had ALK fusions... Molecular profiling upon development of resistance to targeted therapy in our cohort revealed actionable resistance mechanisms for over a third of patients and clinical trial options for 67% . These incremental benefits for patients highlight the importance of routine molecular profiling in the setting of acquired TKI resistance in lung cancer.
Clinical
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RB1 (RB Transcriptional Corepressor 1)
|
TP53 mutation • BRAF V600E • EGFR mutation • BRAF V600 • EGFR T790M • MET amplification • MET exon 14 mutation • ALK fusion • EGFR C797S • ALK mutation • RB1 mutation • MET mutation • ALK G1202R • ALK I1171 • ALK I1171N • BRAF amplification • RB1 mutation + TP53 mutation
|
Tagrisso (osimertinib)
9ms
[VIRTUAL] Next generation sequencing of sarcomas: Response to crizotinib in two cases with MET amplification. (ASCO 2021)
Several rare and novel fusions were identified; a sarcoma with TPM4-NTRK3 fusion responded to larotrectinib, while a sarcoma with PML-JAK1 fusion did not respond to ruxolitinib, and a sarcoma with IL7R-BCL2 fusion progressed on venetoclax . NGS profiling led to a targeted therapy with a clinical benefit rate of 12% in this cohort . NGS profiling led to a change in diagnosis in 5% of this cohort . Multi-institutional collaborations to track outcomes of matched therapy would help determine the utility of therapies in rare cancers and unusual alterations.
Clinical • Next-generation sequencing • Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • BCL2 (B-cell CLL/lymphoma 2) • JAK1 (Janus Kinase 1) • IL7R (Interleukin 7 Receptor) • TPM4 (Tropomyosin 4)
|
TMB-H • NTRK3 fusion • MET amplification • IL7R-BCL2 fusion • PML-JAK1 fusion • TPM4-NTRK3 fusion • BCL2 fusion
|
Venclexta (venetoclax) • Xalkori (crizotinib) • Vitrakvi (larotrectinib) • Jakafi oral (ruxolitinib)
9ms
[VIRTUAL] Tepotinib in patients (pts) with advanced non-small cell lung cancer (NSCLC) with MET amplification (METamp). (ASCO 2021)
In the first study of a MET inhibitor in NSCLC with METamp prospectively detected by liquid biopsy, tepotinib showed high and clinically meaningful activity, especially in 1L, and was generally well tolerated . Tepotinib warrants further evaluation in NSCLC with METamp.
Clinical
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
|
Guardant360® CDx
|
Tepmetko (tepotinib)
9ms
[VIRTUAL] Phase II two-arm study of tepotinib plus osimertinib in patients with EGFR-mutant NSCLC and acquired resistance to first-line osimertinib due to MET amplification: INSIGHT 2. (ASCO 2021)
In the INSIGHT study (NCT01982955), the combination of tepotinib and the EGFR TKI gefitinib improved outcomes in patients with EGFR-mutant METamp NSCLC and EGFR TKI resistance compared to chemotherapy (INSIGHT) . Approximately 100 sites in 17 countries in Europe, Asia, and North America are expected to participate . Approximately 15 sites will recruit patients in the US.
Clinical • P2 data • Preclinical
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification
|
Tagrisso (osimertinib) • gefitinib • Tepmetko (tepotinib)
9ms
[VIRTUAL] Mutational analysis of rare insertions and deletions in exon 18 and 19 of HER2 in Chinese patients with different cancer types. (ASCO 2021)
Dose-response curves showed inhibitory effects on cell viability of several HER2 tyrosine kinase inhibitors including neratinib, lapatinib, poziotinib and afatinib . Our study revealed a novel class of HER2 KD indels in exon 18/19 that may act as driver mutations in several cancer types . The drug response observed in vitro indicated the potential to use anti-HER2 targeted therapies for HER2 exon 18/19 indels . Further studies on this rare type of HER2 mutation are warranted.
Clinical
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR exon 20 insertion • HER-2 exon 20 insertion • MET mutation • EGFR exon 18 mutation • MET amplification + EGFR mutation • HER-2 exon 20 mutation
|
Gilotrif (afatinib) • lapatinib • Nerlynx (neratinib) • poziotinib (HM 78136B)
9ms
Enrollment change • Enrollment closed
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
|
Oncomine™ Comprehensive Assay v3M
9ms
MErCuRIC1: MEK and MET Inhibition in Colorectal Cancer (clinicaltrials.gov)
P1, N=82, Completed, University of Oxford | Active, not recruiting --> Completed
Clinical • Trial completion
|
KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET overexpression • MET mutation • MET expression
|
Xalkori (crizotinib) • Mektovi (binimetinib) • mirdametinib (PD-0325901)
9ms
Utility of Circulating Tumor DNA in Identifying Somatic Mutations and Tracking Tumor Evolution in Patients with Non-small Cell Lung Cancer. (PubMed, Chest)
Although ctDNA exhibited similar utility to tissue biopsies, more mutations in targetable genes were missed in tissue biopsies. Therefore, the evaluation of ctDNA in conjunction with tissue biopsies may help to detect additional targetable mutations to improve clinical outcomes in advanced NSCLC.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDK6 (Cyclin-dependent kinase 6)
|
KRAS mutation • EGFR mutation • BRAF mutation • MET amplification • BRAF amplification • CDK6 amplification
9ms
Crizotinib for c-MET-amplified advanced NSCLC: a single-center experience. (PubMed, Tumori)
Crizotinib is an effective treatment option other than cytotoxic chemotherapy in the limited number of patients with MET amplification in the stage 4 lung adenocarcinoma subgroup. It is important to investigate this amplification, which can be detected especially in smoking patients in the appropriate patient group, and to use appropriate tyrosine kinase inhibitors in treatment.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET mutation
|
Xalkori (crizotinib)
9ms
The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSé-Crizotinib Program. (PubMed, Target Oncol)
Large-scale screening for MET-amplified esogastric adenocarcinomas is feasible. MET amplification was observed in 5.5% of gastric and 12.8% of esophageal adenocarcinomas. Crizotinib shows encouraging results in selected patients. Thus, c-MET inhibition for MET-amplified tumors deserves further evaluation.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET expression
|
Xalkori (crizotinib)
9ms
Efficacy and safety of crizotinib plus bevacizumab in ALK/ROS-1/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study. (PubMed, Am J Transl Res)
This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive ALK rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ROS-1/c-MET positive NSCLC patients.
Clinical • Observational data • Journal
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • ALK positive • ALK rearrangement • ROS1 positive • ROS1 fusion • MET positive
|
Avastin (bevacizumab) • Xalkori (crizotinib)
9ms
Capmatinib in Japanese patients with MET exon 14 skipping-mutated or MET-amplified advanced NSCLC: GEOMETRY mono-1 study. (PubMed, Cancer Sci)
Common treatment-related adverse events among the 45 Japanese patients were blood creatinine increased (53.3%), nausea (35.6%), and oedema peripheral (31.1%); most were grade 1/2 severity. In conclusion, capmatinib was effective and well tolerated by Japanese patients with METΔex14/MET-amplified NSCLC, consistent with the overall population.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation
|
Tabrecta (capmatinib)
10ms
Chasing the Target: New Phenomena of Resistance to Novel Selective RET Inhibitors in Lung Cancer. Updated Evidence and Future Perspectives. (PubMed, Cancers (Basel))
The potent, RET-selective tyrosine kinase inhibitors (TKIs) pralsetinib and selpercatinib, are effective against the RET V804L/M gatekeeper mutants, however, adaptive mutations that cause resistance at the solvent front RET G810 residue have been found, pointing to the need for the development of the next-generation of RET-specific TKIs. Also, as seen in EGFR- and ALK-driven NSCLC, the rising of the co-occurring amplifications of KRAS and MET could represent other escaping mechanisms from direct inhibition. In this review, we summarize actual knowledge on RET fusions, focusing on those involved in NSCLC, the results of main clinical trials of approved RET-inhibition drugs, with particular attention on recent published results of selective TKIs, and finally, pre-clinical evidence regarding resistance mechanisms and suggestion on hypothetical and feasible drugs combinations and strategies viable in the near future.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
|
MET amplification • RET fusion • KRAS amplification • RET V804L • RET V804*
|
Retevmo (selpercatinib) • Gavreto (pralsetinib)
10ms
Effect of High-fat Meal on the Pharmacokinetics of TQ-B3139 Capsules (clinicaltrials.gov)
P1, N=12, Recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting --> Recruiting | Trial primary completion date: Mar 2021 --> Mar 2022
Clinical • Enrollment open • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • ALK fusion • ALK mutation • ROS1 fusion • MET mutation • ALK-ROS1 fusion
|
TQ-B3139
10ms
Study of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal Cancer (PERSPECTIVE) (clinicaltrials.gov)
P2, N=48, Recruiting, EMD Serono Research & Development Institute, Inc. | Not yet recruiting --> Recruiting
Clinical • Enrollment open • Preclinical
|
BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
Erbitux (cetuximab) • Tepmetko (tepotinib)
10ms
Clinical • New P3 trial • Combination therapy
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR T790M negative
|
cisplatin • Tagrisso (osimertinib) • carboplatin • pemetrexed • Tabrecta (capmatinib)
10ms
Exploring the resistance mechanisms of second-line osimertinib and their prognostic implications using next-generation sequencing in patients with non-small-cell lung cancer. (PubMed, Eur J Cancer)
Loss of the T790M mutation was associated with early resistance to osimertinib, and this was exacerbated by MET amplification. Further work is needed to fully understand the implications of each resistance mechanism.
Clinical • Journal • Next-generation sequencing
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
|
KRAS mutation • EGFR mutation • PIK3CA mutation • EGFR T790M • MET amplification • RET fusion • EGFR C797S • RET mutation • MET mutation • EGFR mutation + PIK3CA mutation
|
Tagrisso (osimertinib)
10ms
Volitinib in Treating Patients With Recurrent or Refractory Primary CNS Tumors (clinicaltrials.gov)
P1, N=50, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
Clinical • Trial suspension
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET mutation • MET fusion • HGF amplification
|
Orpathys (savolitinib)
10ms
MET deletion is a frequent event in gastric/gastroesophageal junction/esophageal cancer: a cross-sectional analysis of gene status and signal distribution in 1,580 patients. (PubMed, Ann Transl Med)
The screening data from this cross-sectional study showed that MET deletion and amplification are frequent events in G/GEJ/E cancer, which are linked to different phenotypical signal distribution patterns. The role of MET deletion in relation to tumor development is not fully understood but it is likely to play a role in the oncogenic transformation of the cells.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
10ms
ADVL1622: Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors (clinicaltrials.gov)
P2, N=146, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Sep 2021 --> Jun 2021
Clinical • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • AXL (AXL Receptor Tyrosine Kinase)
|
MET amplification • MET overexpression • RET mutation • RET rearrangement • MET mutation • AXL overexpression
|
Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
10ms
Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1. (PubMed, Acta Biochim Biophys Sin (Shanghai))
c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
PD-L1 expression • HER-2 positive • HER-2 amplification • HER-2 negative • MET amplification • MET expression • HER-2 amplification + PD-L1 expression
10ms
[VIRTUAL] Acquired resistance in patients with EGFRm NSCLC following treatment with osimertinib plus savolitinib in the Ph1b TATTON study Parts B and D (AACR 2021)
In this analysis, approximately half of all evaluable pts had an identifiable acquired resistance mechanism; resistance appeared to be predominantly mediated by either MET, EGFR or KRAS. Co-occurring mutations across multiple genes were rarely detected. However, multiple acquired mutations were often detected in a specific gene, particularly MET, suggesting individual tumors showed inherent resistance dependencies.
Preclinical • Clinical
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
KRAS mutation • EGFR mutation • EGFR T790M • MET amplification • EGFR amplification • PIK3CA E545K • MET mutation • KRAS G13 • KRAS G12 • PIK3CA E545 • EGFR T790M negative
|
Guardant360® CDx
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
10ms
[VIRTUAL] MET alterations are enriched in lung adenocarcinoma brain metastases and define a distinct molecular and transcriptomic subtype (AACR 2021)
Together, we show that over a third of LUAD BM patients have MET alterations compared to primary LUAD and may be responsive to MET inhibitors. Further, our liquid biopsy approach may allow us to identify BM-specific alterations for patient selection in clinical trials.
KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • MET (MET proto-oncogene, receptor tyrosine kinase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • RB1 (RB Transcriptional Corepressor 1) • SMAD4 (SMAD family member 4)
|
IDH1 mutation • MET amplification • MET exon 14 mutation • MET expression • MET-H
|
Guardant360® CDx
10ms
[VIRTUAL] The bispecific antibody MCLA-129 impairs NSCLC tumor growth by targeting EGFR and c-MET, inhibiting ligand-induced signaling and promoting ADCC and ADCP (AACR 2021)
In addition, in an acquired erlotinib EGFR TKI resistance model, treatment of mice harboring tumors as big as >500 mm3 led to significant reduction of tumor size which persisted after the treatment period.Taken together these data demonstrate that MCLA-129 is a potent inhibitor of tumor growth applying various mechanisms of action, including inhibition of c-MET and EGFR signaling, ADCC and ADCP. MCLA-129 holds promise as a potential treatment for patients with NSCLC and other cancers, and warrants clinical evaluation.
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR L858R • EGFR T790M • MET amplification • MET expression • EGFR H1975 • EGFR E746
|
erlotinib • MCLA-129
10ms
[VIRTUAL] Efficacy of amivantamab, a bispecific EGFR/MET antibody, correlates with EGFR expression and signaling in NSCLC models with wild-type EGFR (AACR 2021)
The lack of species cross-reactivity with the MET ligand HGF, likely underestimates MET signaling dependencies in these mouse models, although this may play a role in patient tumors. These findings suggest NSCLC patients with elevated wt EGFR expression and lacking driver mutations may achieve therapeutic benefit from amivantamab treatment.
Clinical
|
KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
KRAS mutation • MET amplification • EGFR amplification • MET mutation • MET expression
|
Rybrevant (amivantamab-vmjw)
10ms
[VIRTUAL] Trastuzumab deruxtecan (T-DXd) sensitivity in various levels of HER2 expressing gastric cancer cells (AACR 2021)
Currently, the evaluation of the underlying mechanisms is ongoing. Our results indicate that T-DXd shows efficacy in HER2-amplified GC cell lines, HER2 moderate/low-expression, and some cell lines with HER2 non-expression.
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRG1 (Neuregulin 1)
|
HER-2 positive • HER-2 negative • MET amplification • HER-2 expression • HER-2-H
|
Enhertu (fam-trastuzumab deruxtecan-nxki)
10ms
[VIRTUAL] Mechanisms of acquired resistance to KRAS G12C inhibition in cancer (AACR 2021)
In early phase clinical trials of patients with KRASG12C-mutant cancers, promising antitumor activity has been reported with drugs such as adagrasib (MRTX849) and sotorasib (AMG510) which are direct inhibitors of KRASG12C. Diverse genomic and histologic mechanisms impart resistance to covalent KRASG12C inhibitors in patients with cancer. Acquired genomic mutations, amplifications, and rearrangements may be potentially targetable by combining KRASG12C inhibition with available kinase inhibitors or SHP2 inhibitors.
Preclinical • Late-breaking abstract
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • FGFR (Fibroblast Growth Factor Receptor)
|
BRAF V600E • KRAS mutation • EGFR mutation • NRAS mutation • BRAF V600 • MET amplification • EGFR amplification • KRAS G13D • NRAS Q61K • RET M918T • KRAS G13 • KRAS amplification • NRAS G13 • NRAS Q61 • BRAF amplification • KRAS Q61K • MAP2K1 K57N
|
Lumakras (sotorasib) • adagrasib (MRTX849)
10ms
[VIRTUAL] BYON3521, a novel effective and safe c-Met targeting antibody-drug conjugate (AACR 2021)
In all, BYON3521 was deemed a safe ADC with potential for clinical benefit in patients. Preparations are ongoing to start clinical Phase I in 2021.
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET expression • MET-H
|
BYON3521
10ms
[VIRTUAL] Role of emt biomarkers in mediating osimertinib resistance in non-small cell lung cancer (AACR 2021)
Immunofluorescence studies in H1975OR cells for expression of PRMT1 showed that there was 3.18 fold increase as compared to 2.21 fold increase in Erlotinib resistant H1975 (H1975ER) and 4.77 fold increase in H3255OR as compared to 2.27 fold increase in H3255ER. In conclusion, biomarkers like PRMT1 may mediate the process of EMT by methylation of Twist1 and upregulation of p120 that prevents transcriptional repression of Kaiso factor target genes, promoting EMT in OR and ER resistant cells. p-120 expression was found to be higher in smokers compared to quit/nonsmokers indicating that it may have a potential role in lung cancer.
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDH1 (Cadherin 1) • PRMT1 (Protein Arginine Methyltransferase 1)
|
EGFR mutation • MET amplification • ALK rearrangement • EGFR C797S • MET mutation • EGFR H1975
|
erlotinib • Tagrisso (osimertinib)
10ms
SATB1-Mediated Upregulation of the Oncogenic Receptor Tyrosine Kinase HER3 Antagonizes MET Inhibition in Gastric Cancer Cells. (PubMed, Int J Mol Sci)
Concomitantly, SATB1 knockdown prevented upregulation of HER3, thus abrogating the HRG-promoted rescue from MET inhibition. Taken together, our results introduce the combined HER3/MET inhibition as strategy to overcome resistance towards MET inhibitors.
Journal
|
ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • SATB1 (SATB Homeobox 1)
|
MET amplification
10ms
Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion-Positive Lung Cancer. (PubMed, Clin Cancer Res)
ROS1 mutations mediate resistance to crizotinib and lorlatinib in over one-third of cases, underscoring the importance of developing next-generation ROS1 inhibitors with potency against these mutations including G2032R and L2086F. Continued efforts are needed to elucidate ROS1-independent resistance mechanisms.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
|
NRAS mutation • KRAS G12C • MET amplification • ROS1 positive • ROS1 fusion • KRAS G12 • KRAS amplification • ROS1 G2032R • NRAS G12 • ROS1 mutation • ROS1 D2033N • ROS1 S1986F
|
Xalkori (crizotinib) • Rozlytrek (entrectinib) • Lorbrena (lorlatinib) • Cabometyx (cabozantinib tablet)
10ms
PLEKHA5 regulates the survival and peritoneal dissemination of diffuse-type gastric carcinoma cells with Met gene amplification. (PubMed, Oncogenesis)
Mechanistically, PLEKHA5 knockdown dysregulates glycolytic metabolism, leading to activation of the JNK pathway that promotes apoptosis. These results indicate that PLEKHA5 is a novel downstream effector of amplified Met and is required for the malignant progression of Met-addicted DGC.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
11ms
Phase 1 study of telisotuzumab vedotin in Japanese patients with advanced solid tumors. (PubMed, Cancer Med)
In conclusion, telisotuzumab vedotin demonstrated a manageable safety profile, with antitumor activity in Japanese patients with advanced solid tumors; the recommended phase 2 dose was confirmed as 2.7 mg/kg every 3 weeks. ClinicalTrials.gov registration number: NCT03311477.
Clinical • P1 data • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET overexpression
|
telisotuzumab vedotin (ABBV-399) • telisotuzumab (h224G11)
11ms
Crizotinib in Patients With MET-Amplified NSCLC. (PubMed, J Thorac Oncol)
Patients with high-level, MET-amplified NSCLC responded to crizotinib with the highest ORR. Use of combined diagnostics for MET and other oncogenes may potentially identify patients most likely to respond to crizotinib.
Clinical • Journal
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
KRAS mutation • EGFR mutation • BRAF mutation • MET amplification • MET exon 14 mutation
|
Xalkori (crizotinib)
11ms
Tepotinib With Gefitinib in Participants With Locally Advanced or Metastatic NSCLC (INSIGHT) (clinicaltrials.gov)
P1/2, N=88, Active, not recruiting, Merck KGaA, Darmstadt, Germany | Trial completion date: Dec 2020 --> Oct 2021
Clinical • Preclinical • Trial completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET overexpression • EGFR T790M negative
|
cisplatin • gefitinib • carboplatin • pemetrexed • Tepmetko (tepotinib)
11ms
Targeting MET amplification with crizotinib in a case of sinonasal undifferentiated carcinoma. (PubMed, Cancer Invest)
The patient was treated with crizotinib, a tyrosine kinase inhibitor that targets c-MET, and experienced a complete response. Our report demonstrates the potential of employing precision oncology approaches in SNUC and other rare cancers.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
Xalkori (crizotinib)
11ms
Novel Resistance Mechanisms to Osimertinib Analysed by Whole-Exome Sequencing in Non-Small Cell Lung Cancer. (PubMed, Cancer Manag Res)
EGFR C797S mutation and MET amplification are leading mechanisms for osimertinib resistance in lung cancer. The crucial potential mutated genes defined in our present study may need further validation in a considerable number of lung cancer patients.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ABCC1 (ATP Binding Cassette Subfamily C Member 1)
|
EGFR mutation • MET amplification • EGFR C797S • MET mutation
|
Tagrisso (osimertinib)
11ms
TOTEM: Phase I Study of Repotrectinib and Osimertinib in NSCLC Patients (clinicaltrials.gov)
P1, N=32, Not yet recruiting, Instituto Oncológico Dr Rosell
Clinical • New P1 trial
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • NTRK (Neurotrophic receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification • EGFR C797S • EGFR exon 18 mutation
|
Tagrisso (osimertinib) • repotrectinib (TPX-0005)
11ms
[VIRTUAL] Prevalence of MET exon 14-mutations or MET amplification in non-small cell lung cancer in Swiss patients (ELCC 2021)
High MET expression does not enrich for MET exon 14 mutations. However, MET IHC seems to be a cost-effective approach for pre-screening NSCLC for further MET FISH analysis
Clinical
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • MET exon 14 mutation • MET mutation • MET expression • MET-H
11ms
[VIRTUAL] False positive errors in RNA based next generation sequencing of exon 14 skipping mutations in NSCLC (ELCC 2021)
All true positive cases had exon 3 and exon 15 fusion as the sole abnormality. Cases with MET amplification were also negative on sanger sequencing.Conclusions RNA based exon 13 and exon 15 fusion for detection of exon 14 skipping mutations can have false positive calls by Ion torrent-based sequencing and should be confirmed by alternate Methods
Next-generation sequencing
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • KIF5B (Kinesin Family Member 5B) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
|
MET amplification • EGFR amplification • RET fusion • MET exon 14 mutation • MET mutation • KRAS deletion
|
Oncomine Focus Assay
11ms
KRAS G12C-mutant non-small-cell lung cancer: biology, developmental therapeutics, and molecular testing. (PubMed, J Mol Diagn)
These agents include sotorasib (AMG 510), adagrasib (MRTX 849), and JNJ-74699157. In addition to testing for known actionable oncogenic driver alterations in EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, RET, and NTRK and for expression of PD-L1, pathologists, medical oncologists, and community practitioners will need to incorporate routine testing for emerging biomarkers such as MET amplification, ERBB2 (HER2), and KRAS mutations, particularly KRAS G12C, considering the promising development of direct inhibitors of KRAS protein.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
|
PD-L1 expression • KRAS mutation • HER-2 amplification • KRAS G12C • MET amplification • HER-2 mutation • MET exon 14 mutation • KRAS G12 • HER-2 amplification + PD-L1 expression • RET expression • NTRK expression
|
Lumakras (sotorasib) • adagrasib (MRTX849) • JNJ-74699157
11ms
The FAM3C locus that encodes interleukin-like EMT inducer (ILEI) is frequently co-amplified in MET-amplified cancers and contributes to invasiveness. (PubMed, J Exp Clin Cancer Res)
These novel findings suggest MET amplifications are often in reality MET-FAM3C co-amplifications with tight functional cooperation. Therefore, the clinical relevance of this frequent cancer amplification hotspot, so far dedicated purely to c-MET function, should be re-evaluated to include ILEI as a target in the therapy of c-MET-amplified human carcinomas.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • CDH1 (Cadherin 1) • MMP9 (Matrix metallopeptidase 9)
|
MET amplification • CDH1 expression • MET-H
11ms
Cell Line Models for Acquired Resistance to First-Line Osimertinib in Lung Cancers-Applications and Limitations. (PubMed, Cells)
Although few clinical data are available about AR mechanisms that arise when osimertinib is used as a first-line therapy, many research groups have established cell lines with AR to osimertinib and have reported on their AR mechanisms. In this review, we summarize the findings on AR mechanisms against first-line osimertinib obtained from analyses of cell line models.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification • MET mutation
|
Tagrisso (osimertinib)
12ms
Clinical • New P1/2 trial • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET fusion
|
Tepmetko (tepotinib)
12ms
TATIN: ctDNA Guided Treatment of Early Resistance to Targeted Treatment (clinicaltrials.gov)
P=N/A, N=30, Recruiting, The Netherlands Cancer Institute | Phase classification: P2 --> P=N/A | Trial completion date: Oct 2020 --> Oct 2021 | Trial primary completion date: Oct 2020 --> Oct 2021
Clinical • Phase classification • Trial completion date • Trial primary completion date • Circulating tumor DNA
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion
|
Xalkori (crizotinib) • Tagrisso (osimertinib)
12ms
Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer. (PubMed, Oncologist)
The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • KDR (Kinase insert domain receptor)
|
MET amplification
|
Avastin (bevacizumab) • Vectibix (panitumumab) • oxaliplatin • Cabometyx (cabozantinib tablet) • irinotecan
12ms
SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov)
P2, N=259, Recruiting, AstraZeneca | Active, not recruiting --> Recruiting | N=192 --> 259
Clinical • Enrollment open • Enrollment change
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR amplification • MET overexpression
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
1year
Molecular mechanism and pharmacokinetics of flavonoids in the treatment of resistant EGFR-mutated non-small-cell lung cancer: a narrative review. (PubMed, Br J Pharmacol)
The current review aims at summarizing the association between the anti-cancer potentials of flavonoids and their possible regulatory roles in certain types of mutation that could trigger EGFR-TKI resistance in NSCLC. Potential practical applications of these phytochemicals, as well as the relevant pharmacokinetics, were also discussed.
PK/PD data • Review • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification
1year
Clinical • New trial • Tumor Mutational Burden • Circulating tumor DNA
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
|
BRAF V600E • EGFR mutation • HER-2 amplification • BRAF V600 • MET amplification • ALK rearrangement • MET exon 14 mutation • RET mutation • RET rearrangement • ROS1 rearrangement • MET mutation • MET amplification + MET Exon 14 mutation
1year
Co-stimulatory and co-inhibitory immune markers in solid tumors with MET alterations. (PubMed, Future Sci OA)
CD6, CCL19, CD40LG, XCR1, MAGEA1, ATM and CCL19 genes were significantly differentially expressed in MET-altered cancers. MET alterations may have a role in various solid tumors as potential therapeutic targets and combination therapy candidates with immune checkpoint inhibitors.
Journal • IO biomarker
|
MET (MET proto-oncogene, receptor tyrosine kinase) • CCL19 (C-C Motif Chemokine Ligand 19) • CD40LG (CD40 ligand)
|
MET amplification • MET exon 14 mutation • MET mutation • MET expression
1year
Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov)
P1a, N=57, Completed, Symphogen A/S | Active, not recruiting --> Completed
Clinical • Trial completion
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
Sym015
1year
Antiproliferative effect, alteration of cancer cell cycle progression and potential MET kinase inhibition induced by 3,4-dihydropyrimidin-2(1H)-one C5 amide derivatives. (PubMed, Eur J Pharmacol)
Molecular docking and dynamics simulation studies confirmed the interaction of compound 23 with the active site of the MET receptor. These findings demonstrate that 3,4-dihydropyrimidin-2(1H)-one analogues may represent promising targeted anticancer agents.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
1year
REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=111, Recruiting, Regeneron Pharmaceuticals | Trial completion date: Feb 2024 --> Nov 2023 | Trial primary completion date: Feb 2024 --> Nov 2023
Clinical • Trial completion date • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET mutation • MET expression
|
REGN5093
1year
Treatment of Non-Small-Cell Lung Cancer Based on Circulating Cell-Free DNA and Impact of Variation Allele Frequency. (PubMed, Clin Lung Cancer)
Initiation of targeted therapy for advanced NSCLC was feasible based only on identification of actionable mutations by cfDNA testing in 9% of the cases for which tissue diagnosis could not be obtained. Actionable targets were identified by cfDNA in 20% of the samples sent at diagnosis. A substantial number of patients benefited from cfDNA testing at initial diagnosis because it identified actionable mutations that led to appropriate targeted treatments.
Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • CD74 (CD74 Molecule) • KIF5B (Kinesin Family Member 5B) • NTRK (Neurotrophic receptor tyrosine kinase)
|
EGFR L858R • MET amplification • EGFR exon 19 deletion • RET fusion • MET exon 14 mutation • EML4-ALK fusion • ALK fusion • KIF5B-RET fusion • EGFR L861Q • ROS1 fusion • EGFR L861R • ALK-ROS1 fusion • NTRK fusion
|
Guardant360® CDx
1year
Combination of tissue and liquid biopsy molecular profiling to detect transformation to small cell lung carcinoma during osimertinib treatment. (PubMed, Ther Adv Med Oncol)
SCLC transformation was linked to the presence of several concomitant gene alterations, including EGFR, TP53 and RB1, but also to specific signal bypass, such as EGFR and MET amplifications and activation of the PI3K/AKT/mTOR pathway. Our report emphasizes the mutational landscape of SCLC histological transformation and highlights the importance of combining tissue and liquid biopsy profiling before and during osimertinib treatment to predict such histological transformation.
Journal • Liquid biopsy
|
TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RB1 (RB Transcriptional Corepressor 1)
|
EGFR mutation • MET amplification
|
Tagrisso (osimertinib)
1year
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET mutation • MET amplification + EGFR mutation
|
gefitinib • Tabrecta (capmatinib)
1year
Tumor Analyses Reveal Squamous Transformation and Off-Target Alterations As Early Resistance Mechanisms to First-line Osimertinib in EGFR-Mutant Lung Cancer. (PubMed, Clin Cancer Res)
Histologic transformation and other off-target molecular alterations are frequent early emerging resistance mechanisms to osimertinib and are associated with poor clinical outcomes.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGF (Fibroblast Growth Factor)
|
KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • MET amplification • RET fusion • RET mutation • MET mutation • BRAF fusion • EGFR G724S • EGFR mutation + PIK3CA mutation • BRAF amplification • FGF amplification
|
Tagrisso (osimertinib)
1year
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR G719S • EGFR L747S
|
Xalkori (crizotinib)
1year
Mechanisms of Resistance to Selective RET Tyrosine Kinase Inhibitors in RET Fusion-Positive Non-Small Cell Lung Cancer. (PubMed, Ann Oncol)
RET solvent front mutations are a recurrent mechanism of RET inhibitor resistance, although they occurred at a relatively low frequency. The majority of resistance to selective RET inhibition may be driven by RET-independent resistance such as acquired MET or KRAS amplification. Next-generation RET inhibitors with potency against RET resistance mutations and combination strategies are needed to effectively overcome resistance in these patients.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
|
KRAS mutation • MET amplification • RET fusion • RET mutation • RET positive
|
Retevmo (selpercatinib) • Gavreto (pralsetinib)
1year
FISH patterns of ROS1, MET, and ALK with a correlation of ALK immunohistochemistry in lung cancer: a case for introducing ALK immunohistochemistry 'Equivocal' interpretation category in the Ventana anti-ALK (D5F3) CDx assay - A tertiary cancer center experience. (PubMed, Indian J Cancer)
An ALK IHC "equivocal" interpretation category should be incorporated into practice. Atypical patterns of ROS1 and genomic heterogeneity need to be evaluated further for any clinical relevance.
Journal • Clinical
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • ALK positive • ALK rearrangement • ALK mutation • ROS1 positive • ROS1 rearrangement • MET mutation • EGFR negative • ALK amplification
|
VENTANA ALK (D5F3) CDx Assay
1year
Volitinib in Treating Patients With Recurrent or Refractory Primary CNS Tumors (clinicaltrials.gov)
P1, N=50, Recruiting, National Cancer Institute (NCI) | N=36 --> 50
Clinical • Enrollment change
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET mutation • MET fusion • HGF amplification
|
Orpathys (savolitinib)
1year
New P1 trial • PARP Biomarker
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
MET amplification • MET mutation • ALK translocation • MET expression • MET-H
|
Xalkori (crizotinib) • Ibrance (palbociclib) • Talzenna (talazoparib) • Inlyta (axitinib)
1year
Comprehensive routine diagnostic screening to identify predictive mutations, gene amplifications, and microsatellite instability in FFPE tumor material. (PubMed, BMC Cancer)
We developed a comprehensive workflow for predictive analysis of diagnostic tumor samples. The smMIP-based NGS analysis was shown suitable for limited amounts of histological and cytological material. As smMIP technology allows easy adaptation of panels, this approach can comply with the rapidly expanding molecular markers.
Journal • Microsatellite instability • MSi-H Biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
|
MSI-H/dMMR • HER-2 amplification • BRAF mutation • MET amplification • HER-2 mutation • FGFR1 amplification • KIT mutation • MET mutation
1year
Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis. (PubMed, BMC Cancer)
Our study demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment.
Preclinical • Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDH1 (Cadherin 1) • VIM (Vimentin)
|
HER-2 amplification • EGFR T790M • MET amplification • HER-2 mutation • MET mutation • CDH1 expression • VIM expression
|
cisplatin • gefitinib • etoposide IV • pemetrexed
1year
Targeted inhibition of c-MET by podophyllotoxin promotes caspase-dependent apoptosis and suppresses cell growth in gefitinib-resistant non-small cell lung cancer cells. (PubMed, Phytomedicine)
These results suggest the potential of PPT as a c-MET inhibitor to overcome tyrosine kinase inhibitor resistance in lung cancer.
Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • BIRC5 (Baculoviral IAP repeat containing 5) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1)
|
MET amplification • MCL1 expression • BIRC5 expression • CDKN1B expression
|
gefitinib
1year
Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study. (PubMed, South Asian J Cancer)
All patients received first-line chemotherapy with gemcitabine-cisplatin regimen. Patients with ERBB2/3 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with MET amplification were treated with crizotinib...ERBB3 mutation showed response to lapatinib. MET and PIK3 are new findings in GBC, which may be targeted.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • FGFR (Fibroblast Growth Factor Receptor)
|
HER-2 amplification • MET amplification • HER-2 mutation • MET mutation • ERBB3 mutation
|
Herceptin (trastuzumab) • Xalkori (crizotinib) • cisplatin • gemcitabine • lapatinib • capecitabine • Abraxane (albumin-bound paclitaxel)
1year
Effect of High-fat Meal on the Pharmacokinetics of TQ-B3139 Capsules (clinicaltrials.gov)
P1, N=12, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Clinical • New P1 trial
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • ALK fusion • ALK mutation • ROS1 fusion • MET mutation • ALK-ROS1 fusion
|
TQ-B3139
1year
Metformin Promotes Anti-tumor Biomarkers in Human Endometrial Cancer Cells. (PubMed, Reprod Sci)
In the context of reduced KLF9 expression (by siRNA targeting), MET rapidly amplified PGR, PGR-B, and KLF4 transcript levels. Our findings suggest that MET acts directly in EC cells to modify steroid receptor expression and signaling network and may constitute a preventative strategy against EC in high-risk non-diabetic women.
Journal
|
ER (Estrogen receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • DKK1 (dickkopf WNT signaling pathway inhibitor 1)
|
MET amplification
|
metformin
1year
MET amplification results in heterogeneous responses to osimertinib in EGFR-mutant lung cancer treated with erlotinib. (PubMed, Cancer Sci)
Combination with osimertinib plus crizotinib induced tumor shrinkage in the KNZ_OR xenograft model. Hence, MET amplification might induce heterogeneous responses to osimertinib in EGFR-mutated NSCLC. Further investigations on mutated EGFR and amplified MET might lead to the development of effective therapies.
Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
|
EGFR mutation • EGFR L858R • EGFR T790M • MET amplification • ERBB3 mutation • EGFR positive
|
Xalkori (crizotinib) • erlotinib • Tagrisso (osimertinib)
1year
SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov)
P2, N=192, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
Clinical • Enrollment closed
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR amplification • MET overexpression
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
1year
Osimertinib for Front-Line Treatment of Locally Advanced or Metastatic EGFR-Mutant NSCLC Patients: Efficacy, Acquired Resistance and Perspectives for Subsequent Treatments. (PubMed, Cancer Manag Res)
We then present the most frequent tumor escape mechanisms when osimertinib is prescribed in first line: off-target (MET amplification, HER2 amplification, BRAF mutation, gene fusions, histologic transformation) and on-target mechanisms (EGFR mutation). Finally, we discuss subsequent biomarker-driven treatment strategies.
Clinical • Review • Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 amplification • BRAF mutation • MET amplification • BRAF amplification
|
Tagrisso (osimertinib)
1year
Genetic Heterogeneity of MET-aberrant Non-Small Cell Lung Cancer and its Impact on the Outcome of Immunotherapy. (PubMed, J Thorac Oncol)
METex14, METamp GCN≥10, and METamp GCN<10 represent subgroups of MET-dysregulated NSCLC with distinct molecular and clinical features. METex14 patients do not seem to benefit from immunotherapy in contrast to METamp patients, which is of particular relevance for the prognostically poor METamp GCN≥10 subgroup.
Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
PD-L1 expression • TP53 mutation • KRAS mutation • MET amplification • PD-L1 mutation
1year
Comprehensive analysis of 34 MiT family translocation renal cell carcinomas and review of the literature: investigating prognostic markers and therapy targets. (PubMed, Pathology)
Larger tumour size, the presence of necrosis and MET immunohistochemical expression correlate with aggressive behaviour in Xp11 renal cell carcinomas, especially in combination. VEGF, MET, cathepsin K but not AXL may be potential predictive markers for targeted therapy in MiT family translocation renal cell carcinomas.
Review • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • AXL (AXL Receptor Tyrosine Kinase) • CA9 (Carbonic anhydrase 9) • CD68 (CD68 Molecule)
|
MET amplification • AXL expression • CA9 expression
|
Cabometyx (cabozantinib tablet)
1year
[VIRTUAL] Resistance Mechanisms to Osimertinib Upon it’s Line of Therapy in Patients with EGFR+ NSCLC and Beyond (IASLC-WCLC 2020)
MET amplification was found in a substantial percentage of group A patients raising the possibility of it being a probable resistance mechanism.Compared to patients receiving osimertinib as second line treatment, in treatment naïve patients the C797S is not necessarily a leading resistance mechanism. Combined therapy was effective and well tolerated, making it a decent choice in patients for whom there is a reasonable rationale for such treatment.
Clinical
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • ARID1A (AT-rich interaction domain 1A)
|
KRAS mutation • EGFR mutation • HER-2 amplification • PIK3CA mutation • EGFR T790M • MET amplification • ARID1A mutation • EGFR C797S • MET mutation • KRAS amplification
|
Guardant360® CDx
|
Tagrisso (osimertinib)
1year
[VIRTUAL] Efficacy and Safety of the Novel HER3 Directed Antibody Drug Conjugate Patritumab Deruxtecan (HER3-DXd; U3-1402) in EGFR-mutated NSCLC (IASLC-WCLC 2020)
Median number of prior EGFR TKIs was 2 (range, 1-4); 49 patients [86%] received prior osimertinib. Efficacy was observed in patients with various mechanisms of EGFR TKI resistance, including EGFR C797S mutation, MET amplification, HER2 mutation, BRAF fusion, and PIK3CA mutation. Conclusion Patritumab deruxtecan at 5.6 mg/kg provides promising evidence of preliminary antitumor activity and safety in heavily pre-treated patients with locally advanced or metastatic EGFRm NSCLC.
Clinical
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 amplification • BRAF mutation • PIK3CA mutation • MET amplification • EGFR C797S • MET mutation • ERBB3 expression • BRAF fusion • ERBB3 mutation • EGFR mutation + PIK3CA mutation • BRAF amplification
|
Tagrisso (osimertinib) • patritumab deruxtecan (U3-1402)
1year
[VIRTUAL] Demonstrating VALUE of Liquid Biopsy for Lung Cancer in a Public Healthcare System (IASLC-WCLC 2020)
Mean TAT was 7.7 days (SD+/-1.6) for LB vs 20.8 days (SD+/- 9.8) for TT. Conclusion LB using G360 identifies actionable targets beyond tissue profiling alone in newly diagnosed lung cancer patients, has faster TAT and yields similar outcomes with targeted and non-targeted therapy.
IO biomarker • Liquid biopsy
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
|
HER-2 amplification • KRAS G12C • MET amplification • MET exon 14 mutation • KRAS G12
|
Guardant360® CDx
1year
[VIRTUAL] PAPILLON: Randomized Phase 3 Study of Amivantamab Plus Chemotherapy vs Chemotherapy Alone in EGFR Exon20ins NSCLC (IASLC-WCLC 2020)
The primary objective of this phase 3 randomized, open-label study is to compare the efficacy of amivantamab in combination with chemotherapy (amivantamab/carboplatin/pemetrexed) versus carboplatin/pemetrexed alone as a first-line treatment for patients with EGFR Exon20ins disease. Key secondary endpoints include objective response rate and overall survival. Safety assessments will include monitoring adverse events and laboratory abnormalities.
Clinical • P3 data
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR exon 20 insertion • MET mutation • EGFR exon 20 mutation
|
carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw)
1year
[VIRTUAL] Imipramine Blue (IP) plus MET Tyrosine Kinase Inhibitors (TKI) Suppress Lung Adenocarcinoma (LUAD) KRAS Mutation Tumor Growth (IASLC-WCLC 2020)
Previously, we identified OTSSP167 as a PAK1 kinase inhibitor with significant activity in A549 (KRASG12-C and LKB1nsm)...Cell lines were treated with IP and MET TKIs (crizotinib, savolitinib and tepotinib)...The liaison of MET and LKB1 nsm should be further investigated. LKB1 mRNA expression, together with MET and FOXM1 mRNA expression, warrants assessment in KRAS LUAD patients.
KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • FOXM1 (Forkhead Box M1)
|
TP53 mutation • KRAS mutation • KRAS G12C • MET amplification • MET mutation • MET expression • KRAS expression
|
Xalkori (crizotinib) • Orpathys (savolitinib) • Tepmetko (tepotinib) • OTS167 • imipramine
1year
[VIRTUAL] Targeting the STAT3/PIM Kinase Pathway to Overcome EMT-Mediated Acquired Resistance to EGFR TKIs in NSCLC (IASLC-WCLC 2020)
Third generation Osimertinib, targeting sensitizing EGFR mutations and the T790M resistance mutation, received FDA approval as first-line therapy following data from the Phase III FLAURA trial...The efficacy of pan-PIM inhibitor (AZD1208) & STAT3 inhibitor BBI608 alone and in combination with erlotinib were quantified using the CellTiter-Blue, cell viability assay, in all cell lines...Treatment with pan-PIM inhibitor (AZD1208) alone and in combination with erlotinib resulted in a decrease in protein kinase phosphorylation in Clone 3 including pSTAT3 (Ser727) & pSTAT3 (Tyr705). Conclusion Based on these results, co-targeting PIM and EGFR may provide a therapeutic strategy for circumventing bypass mechanisms of resistance, inhibiting tumor cell motility and migration and blocking the progression and outgrowth of drug resistant cancer cells significantly improving patient prognosis and survival when EGFR is targeted
Preclinical
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AXL (AXL Receptor Tyrosine Kinase) • PIM1 (Pim-1 Proto-Oncogene)
|
EGFR mutation • HER-2 amplification • BRAF mutation • PIK3CA mutation • EGFR T790M • MET amplification • EGFR C797S • MET mutation • MET expression • EGFR L718Q • EGFR mutation + PIK3CA mutation • BRAF amplification
|
erlotinib • Tagrisso (osimertinib) • AZD1208 • napabucasin (BBI608)
1year
[VIRTUAL] Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer (IASLC-WCLC 2020)
Conclusion Amivantamab treatment led to promising efficacy with durable responses in patients with EGFR Exon20ins NSCLC post-platinum doublet and continues to demonstrate a manageable safety profile in over 250 patients treated at the RP2D. A phase 3 study, PAPILLON, evaluating amivantamab in combination with chemotherapy in the front-line setting is in planning stages.
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR exon 20 insertion • MET mutation • EGFR exon 20 mutation
|
Rybrevant (amivantamab-vmjw)
1year
[VIRTUAL] Concurrent EGFR and KRAS Mutations in Lung Adenocarcinoma: A Single Institution Case Series (IASLC-WCLC 2020)
Further studies are necessary to determine the most effective therapeutic strategies to address this unique subset of lung cancer patients. KRAS inhibitors are currently under study.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
PD-L1 expression • KRAS mutation • EGFR mutation • EGFR L858R • MET amplification • KRAS G12D • EGFR exon 21 mutation • KRAS G12 • KRAS G12S • EGFR exon 18 mutation • EGFR mutation + KRAS mutation • KRAS exon 13 mutation
1year
[VIRTUAL] Clinical Characteristics and Outcome of Patients with Non-Small Cell Lung Cancer Harboring BRAF Mutations (IASLC-WCLC 2020)
Most(20/25) of them had chose chemotherapy ± bevacizumab as first line, while the rest accepted other treatment, including 1 chemotherapy combined with pembrolizumab, 3 Icotinib and 1 vandetanib. At the data cutoff of follow-up (July 31, 2020), OS events were 11 (44%), and median OS was 33.9m(3.2m-64.7m). Conclusion The most common genotype of NSCLC with BRAF mutation was V600E mutation, which was more tendency to have a concomitant mutation, the therapeutic response was well, and overall survival data had showed a promising outcomes.
Clinical • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
TP53 mutation • BRAF V600E • EGFR mutation • BRAF mutation • PIK3CA mutation • EGFR L858R • MET amplification • MET mutation • EGFR mutation + PIK3CA mutation
|
Keytruda (pembrolizumab) • Avastin (bevacizumab) • Conmana (icotinib) • Caprelsa (vandetanib)
1year
[VIRTUAL] MET Amplification and Immune Checkpoint Inhibitor Efficacy in NSCLC (IASLC-WCLC 2020)
In addition, drug sensitivity analysis in the GDSC dataset suggested that the MET-amplification group exhibited resistance to common chemotherapeutic and targeted drugs. Conclusion MET amplification was strongly associated with longer PFS times and with known immunotherapeutic response markers, including the TMB, the neoantigen load, immune-related genes, and high infiltration of specific immune cells, suggesting that MET amplification can be used as a novel predictive biomarker in NSCLC immunotherapy.
Clinical • Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
1year
[VIRTUAL] A Phase 1/1b Study of Lazertinib as Monotherapy and in Combination with Amivantamab in Advanced EGFR-Mutated NSCLC (IASLC-WCLC 2020)
The phase 1b expansion cohort A will enroll patients who have progressed on prior treatment with both osimertinib and platinum-doublet chemotherapy, for treatment with the combination of lazertinib and amivantamab. No dose limiting toxicity has been observed, and the safety and tolerability of lazertinib monotherapy at the RP2D was confirmed in Japanese patients. Enrollment into phase 1b expansion cohort A is ongoing.
P1 data • Combination therapy
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification • MET mutation
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
1year
[VIRTUAL] Transformation to Small Cell Lung Cancer from an Adenocarcionma EGFR+ as Resistance Mechanism. Utility of Liquid Biopsy in Treatment Selection (IASLC-WCLC 2020)
Initially received gefitinib 250 mg/day...The therapeutic plan was Radiation therapy in rib cage and 6 cycles of chemotherapy platin based plus etoposide, after complete treatment response assessment (RA) showed stable disease... LB has demonstrated in this patient the coexistence of L858 Mutation in blood and SCLC in tumor tissue. The transformation to SCLC in histological tissue biopsy is a very rare mechanism of resistance to TKIs, about 3 % of the cases of the patients with EGFR mutations. LB allows us to select the best treatment for this patient and could detect the absence of other mechanism of resistance, like mutation of the EGFR T790M.
Liquid biopsy
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 amplification • BRAF mutation • EGFR L858R • EGFR T790M • MET amplification • EGFR exon 20 insertion • EGFR exon 20 mutation
|
Tagrisso (osimertinib) • gefitinib • etoposide IV
1year
[VIRTUAL] Osimertinib + Savolitinib in pts with EGFRm MET-Amplified/Overexpressed NSCLC: Phase Ib TATTON Parts B and D Final Analysis (IASLC-WCLC 2020)
Further exploration of the osimertinib plus savolitinib combination is underway in the SAVANNAH (NCT03778229) and ORCHARD (NCT03944772) studies. Table
Clinical • P1 data
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification • MET overexpression • MET mutation • EGFR mutation + EGFR T790M • EGFR T790M negative
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
1year
[VIRTUAL] Circulating Tumor DNA Analysis in NSCLC with MET exon 14 Skipping Alterations (IASLC-WCLC 2020)
Small molecule inhibitors (crizotinib, tepotinib, capmatinib and savolitinib) have shown efficacy in this patient population. The distribution of alterations of METex14 identified using liquid biopsy were similar to previously reported cohorts from tissue biopsies. Other driver oncogene alterations co-occur with METex14 at a low frequency.
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDK4 (Cyclin-dependent kinase 4) • NTRK (Neurotrophic receptor tyrosine kinase)
|
TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • MET amplification • MET exon 14 mutation • ROS1 fusion • MET mutation • CBL mutation • CDK4 amplification • BRAF amplification • CDK4 mutation • NTRK fusion
|
Guardant360® CDx
|
Xalkori (crizotinib) • Orpathys (savolitinib) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
1year
MET-dependent solid tumours - molecular diagnosis and targeted therapy. (PubMed, Nat Rev Clin Oncol)
By contrast, the therapeutic implications of MET fusions remain underexplored. Here we summarize and evaluate the utility of various diagnostic techniques and the roles of different classes of MET-targeted therapies in cancers with MET amplification, mutation and fusion, and MET overexpression.
Review • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET overexpression • MET exon 14 mutation • MET mutation • MET expression • MET fusion
1year
SHP2 Inhibition Influences Therapeutic Response to Tepotinib in Tumors with MET Alterations. (PubMed, iScience)
An Src homology 2 domain-containing phosphatase 2 (SHP2) inhibitor delayed the emergence of tepotinib resistance and synergized with tepotinib in treatment-naive and tepotinib-resistant cells as well as in xenograft models. Alternative signaling pathways potentially diminish the effect of tepotinib monotherapy, and the combination of tepotinib with an SHP2 inhibitor enables the control of tumor growth in cells with MET genetic alterations.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
|
Tepmetko (tepotinib)
1year
[VIRTUAL] In search of novel synthetic lethality anti-cancer drug targets in intrahepatic cholangiocarcinoma: MTAP genomic loss. (ASCO-GI 2021)
Comprehensive genomic profiling elucidated that MTAP GA are frequent in IC and features relatively high GA/tumor, including 9p21 co-deletion, but relatively low TMB and PD-L1 expression. Isolated MTAP deletion without CDKN2A/B co-deletion was extremely rare. In addition to the potential targeting of PRMT5 in MTAP-IC tumors, co-altered genes known to be targets in IC such as FGFR2, IDH1 and BRAF are still prevalent in MTAP-IC, indicating potential for combining targeted therapies in some MTAP-IC patients.
Tumor Mutational Burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • SMAD4 (SMAD family member 4) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • BRCA (Breast cancer early onset) • PRMT5 (Protein Arginine Methyltransferase 5)
|
PD-L1 expression • TP53 mutation • BRAF V600E • KRAS mutation • MSI-H/dMMR • HER-2 amplification • BRAF V600 • KRAS G12C • MET amplification • PD-L1 underexpression • CDKN2A deletion • PD-L1 negative • TMB-L • KRAS G12 • MTAP deletion • CDKN2B deletion • HER-2 amplification + PD-L1 expression • KRAS deletion • miR138 underexpression + miR497 overexpression
|
FoundationOne® CDx • PD-L1 IHC 22C3 pharmDx
1year
[VIRTUAL] Tepotinib plus cetuximab in patients (pts) with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC) and acquired resistance to anti-EGFR antibody therapy due to MET amplification (METamp). (ASCO-GI 2021)
Tepotinib + the EGFR TKI gefitinib demonstrated improved outcomes in pts with EGFR-mutant METamp non-small cell lung cancer and acquired EGFR TKI resistance vs chemotherapy (INSIGHT: NCT01982955). Retrospective assessment of best overall response, DoR and PFS by an independent review committee may be conducted. No formal statistical hypothesis will be tested in this exploratory study.
Clinical
|
BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
Erbitux (cetuximab) • gefitinib • Tepmetko (tepotinib)
1year
[VIRTUAL] Activity of tepotinib in hepatocellular carcinoma (HCC) with high-level MET amplification (METamp): Preclinical and clinical evidence. (ASCO-GI 2021)
One trial enrolled Asian patients (pts) without prior systemic therapy (first line [1L]; NCT01988493) and one enrolled US/European pts with prior sorafenib (second line [2L]; NCT02115373). High-level METamp may be an oncogenic driver in HCC that sensitizes tumors to MET inhibition with tepotinib. Compared with MET overexpression, high-level METamp could be a better predictive biomarker for MET inhibitors in this setting.
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET overexpression
|
Nexavar (sorafenib) • Tepmetko (tepotinib)
1year
MET Amplification (MET/CEP7 Ratio ≥ 1.8) Is an Independent Poor Prognostic Marker in Patients With Treatment-naive Non-Small-cell Lung Cancer. (PubMed, Clin Lung Cancer)
Patients with a MET copy number of ≥ 10 and/or MET/CEP7 ratio of ≥ 1.8 showed significantly poorer survival, and a MET/CEP7 ratio of ≥ 1.8 was an independent poor prognostic factor.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
1year
[VIRTUAL] Rare Mucosal Melanoma With Rapid Deterioration and Unusual Genomic Alterations (ASDP 2020)
Early diagnosis and vigilance is key for proper diagnosis and early intervention, which can be life-saving for this entity. This case has unique genomic alterations, not commonly seen in the cutaneous melanoma.
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ATRX (ATRX Chromatin Remodeler) • SOX10 (SRY-Box 10) • MITF (Melanocyte Inducing Transcription Factor)
|
MET amplification • BRAF amplification
1year
Multiplex RNA-based detection of clinically relevant MET alterations in advanced non-small cell lung cancer. (PubMed, Mol Oncol)
However, FISH failed to identify three patients (30%) with very high MET RNA expression, among which one received MET tyrosine kinase inhibitor treatment deriving clinical benefit. Our results indicate that quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation • MET expression • MET-H
1year
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • KIF5B (Kinesin Family Member 5B)
|
MET amplification
|
Retevmo (selpercatinib)
1year
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • KIF5B (Kinesin Family Member 5B)
|
MET amplification
|
Retevmo (selpercatinib)
1year
SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov)
P2, N=192, Recruiting, AstraZeneca | Trial completion date: Jul 2022 --> Dec 2022
Clinical • Trial completion date
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR amplification • MET overexpression
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
1year
Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • EGFR amplification
1year
Epithelial-to-mesenchymal transition is a resistance mechanism to sequential MET-TKI treatment of MET-amplified EGFR-TKI resistant non-small cell lung cancer cells. (PubMed, Transl Lung Cancer Res)
These cells were subsequently treated with increasing doses of the MET-TKIs capmatinib or crizotinib in combination with erlotinib to establish resistance. EMT is common in the development of sequential EGFR-TKI and MET-TKI resistance in NSCLC cells. Our findings contribute to the evidence of EMT as a common TKI resistance mechanism.
Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR1 (Fibroblast growth factor receptor 1) • CDH1 (Cadherin 1) • VIM (Vimentin) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
|
EGFR mutation • MET amplification • MET mutation • CDH1 expression • FGFR1 expression • VIM expression • ZEB1 expression
|
Xalkori (crizotinib) • erlotinib • Tabrecta (capmatinib)
1year
SRC and PIM1 as potential co-targets to overcome resistance in MET deregulated non-small cell lung cancer. (PubMed, Transl Lung Cancer Res)
We evaluated the activity of class I-II MET inhibitors, the SRC inhibitor dasatinib, and pan-PIM inhibitors in four MET addicted cell lines...We identified a potential role of PIM inhibition in MET amplified tumors and of SRC inhibition in MET addicted tumors. Potential applications of this new treatment strategy warrant further evaluation.
Journal
|
PIM1 (Pim-1 Proto-Oncogene)
|
MET amplification • MET exon 14 mutation
|
dasatinib
1year
Low T790M relative allele frequency indicates concurrent resistance mechanisms and poor responsiveness to osimertinib. (PubMed, Transl Lung Cancer Res)
In patients with progressive NSCLC post 1 generation EGFR-TKI treatment, plasma T790M RAFs of less than 20% can be used to identify patients who carry concurrent resistance mechanisms, and can predict a poorer response to osimertinib. This study was registered on http://www.chictr.org.cn (registration number: ChiCTR-DDD-16007900).
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 amplification • EGFR T790M • MET amplification
|
Tagrisso (osimertinib)
1year
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
|
Xalkori (crizotinib) • erlotinib • Tagrisso (osimertinib)
1year
Acquired MET amplification in non-small cell lung cancer is highly associated with the exposure of EGFR inhibitors and may not affect patients' outcome. (PubMed, Exp Mol Pathol)
Except for EGFR and TP53 mutations, other gene mutations were rare in the patients with MET amplification. Patients with acquired MET amplification showed no significant survival difference comparing to the patients who did not show MET amplification.
Clinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
TP53 mutation • EGFR mutation • MET amplification • MET mutation
1year
Spectrum of Mesenchymal-Epithelial Transition Aberrations and Potential Clinical Implications: Insights From Integrative Pancancer Analysis. (PubMed, Front Oncol)
Esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), and ovarian serous cystadenocarcinoma (OV) had similar characteristics: a high frequency of MET CNVs but relatively few MET mutations, and high MET expression associated with poor prognosis. This study provided significant and comprehensive information regarding MET abnormal expression, alterations (mutations and CNVs), and their clinical associations among 32 cancer types and offered insights into the full MET alteration spectrum and its implications for prognosis and treatment.
Clinical • Journal • Pan Tumor
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET expression • MET-H
1year
[VIRTUAL] Reproducibility of Allelic Fractions of Genomic Variants from Colorectal and Lung Cancer Tissue Downstream of DNA Extraction (AMP 2020)
The study proves greater than 95% reproducibility of allelic frequency using AVENIO tumor tissue kit on a set of 124 clinical FFPET tissue samples. These results are reassuring that NGS methods can be held to high analytical performance standards in clinical laboratory settings to provide physicians with reliable results for cancer patient management. *Research Use Only
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)
|
MET amplification
1year
Clinical impact of uncommon epidermal growth factor receptor exon 19 insertion-deletion variants on epidermal growth factor receptor-tyrosine kinase inhibitor efficacy in non-small-cell lung cancer. (PubMed, Eur J Cancer)
Our results suggest that patients with uncommon EGFR 19delins have improved clinical outcomes with first-generation EGFR inhibitor treatment, but inferior outcomes upon the development of T790M resistance mutations.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR T790M • MET amplification • EGFR exon 19 deletion • EGFR E746
|
Tagrisso (osimertinib)
1year
The novel MET inhibitor, HQP8361, possesses single agent activity and enhances therapeutic efficacy of AZD9291 (osimertinib) against AZD9291-resistant NSCLC cells with activated MET. (PubMed, Am J Cancer Res)
HQP8361 (MK8033) is a novel and selective MET kinase inhibitor that has completed a phase I clinical trial. Moreover, the combination also very effectively inhibited the growth of HCC827/AR xenografts in nude mice. These preclinical findings support the potential of HQP8361 in the treatment of NSCLCs with MET amplification or highly activated MET and, when combined with AZD9291, in overcoming acquired resistance to EGFR-TKIs due to MET amplification.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • MCL1 (Myeloid cell leukemia 1)
|
EGFR mutation • EGFR T790M • MET amplification
|
Tagrisso (osimertinib) • HQP8361 • lovastatin
1year
[VIRTUAL] Her family genes, DDR2 and PI3KCA mutations may be early events in pre-neoplastic lesions and in atypical bronchial type epithelium (ECP 2020)
The AIS case exhibited ERBB2/4, EGFR and SMAD4 somatic mutations while the two MIA cases were sequencing apparently wild-type for the applied panel. Conclusion Mutational status in ABTE identical to concomitant adenocarcinomas provides concern about early genetic events present in lung adenocarcinoma carcinogenesis deserving further studies to be emphasized as pre-neoplastic lesion to lead early clinical guidance for high-risk patients identification in bronchial – pulmonary carcinoma in screening.
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SMAD4 (SMAD family member 4) • NKX2-1 (NK2 Homeobox 1) • DDR2 (Discoidin domain receptor 2) • VIM (Vimentin) • TP63 (Tumor protein 63)
|
KRAS mutation • MET amplification • HER-2 mutation • ALK rearrangement • FGFR2 mutation • ROS1 rearrangement • VIM expression
1year
[VIRTUAL] Her family genes, DDR2 and PI3KCA mutations may be early events in pre-neoplastic lesions and in atypical bronchial type epithelium (ECP 2020)
The AIS case exhibited ERBB2/4, EGFR and SMAD4 somatic mutations while the two MIA cases were sequencing apparently wild-type for the applied panel. Conclusion Mutational status in ABTE identical to concomitant adenocarcinomas provides concern about early genetic events present in lung adenocarcinoma carcinogenesis deserving further studies to be emphasized as pre-neoplastic lesion to lead early clinical guidance for high-risk patients identification in bronchial – pulmonary carcinoma in screening.
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SMAD4 (SMAD family member 4) • NKX2-1 (NK2 Homeobox 1) • DDR2 (Discoidin domain receptor 2) • VIM (Vimentin) • TP63 (Tumor protein 63)
|
KRAS mutation • MET amplification • HER-2 mutation • ALK rearrangement • FGFR2 mutation • ROS1 rearrangement • VIM expression
1year
[VIRTUAL] Her family genes, DDR2 and PI3KCA mutations may be early events in pre-neoplastic lesions and in atypical bronchial type epithelium (ECP 2020)
The AIS case exhibited ERBB2/4, EGFR and SMAD4 somatic mutations while the two MIA cases were sequencing apparently wild-type for the applied panel. Conclusion Mutational status in ABTE identical to concomitant adenocarcinomas provides concern about early genetic events present in lung adenocarcinoma carcinogenesis deserving further studies to be emphasized as pre-neoplastic lesion to lead early clinical guidance for high-risk patients identification in bronchial – pulmonary carcinoma in screening.
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SMAD4 (SMAD family member 4) • NKX2-1 (NK2 Homeobox 1) • DDR2 (Discoidin domain receptor 2) • VIM (Vimentin) • TP63 (Tumor protein 63)
|
KRAS mutation • MET amplification • HER-2 mutation • ALK rearrangement • FGFR2 mutation • ROS1 rearrangement • VIM expression
1year
CHRYSALIS: Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1, N=460, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2022 --> Nov 2023
Clinical • Trial completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion • EGFR exon 20 insertion • MET exon 14 mutation • EGFR C797S • MET mutation • EGFR exon 20 mutation
|
carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
1year
Molecular Insights in Transmission of Cancer From an Organ Donor to Four Transplant Recipients. (PubMed, J Natl Compr Canc Netw)
Because identification of a donor-derived malignancy changes management, our recommendation is to routinely perform short tandem repeat testing (or a comparable assay) immediately upon diagnosis of cancer in any organ transplant recipient. Routine testing for a donor-origin cancer and centralized reporting of outcomes are necessary to establish a robust evidence base for the future development of clinical practice guidelines.
Clinical • Journal
|
CDH1 (Cadherin 1)
|
MET amplification • MET mutation • CDH1 mutation
1year
Management of a patient with a double EGFR and MET anomaly by combined treatment (PubMed, Rev Mal Respir)
This case highlights the efficacy of concomitant treatment in a patient with two oncogenic drivers.
Clinical • Journal • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • MET amplification • MET mutation • MET amplification + EGFR mutation
|
Xalkori (crizotinib) • gefitinib • Imfinzi (durvalumab) • pemetrexed
1year
Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence. (PubMed, Nat Commun)
A second group of recurrent tumors comprises thousands of subclones, has a clonal architecture similar to primary tumors, and is dependent upon the Jak/Stat pathway. Thus the regrowth of dormant tumors proceeds via multiple routes, producing recurrent tumors with distinct clonal composition, genetic alterations, and drug sensitivities.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification
1year
Clinical • New P2 trial • Combination therapy
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • MET amplification • EGFR exon 19 deletion
|
Tagrisso (osimertinib) • Orpathys (savolitinib)
1year
[VIRTUAL] Genomic landscape of IDH-mutant primary glioblastomas shows distinct clinical and molecular features and that CDKN2A should be supplemented with MGMTp and G-CIMP for precise prognostication (SNO 2020)
There were few EGFR amplifications (2/53, 4%), which was different from regular glioblastomas. RNA sequencing (n= 42) showed few fusions (4/42, 10%), which was different from IDH-mutant secondary glioblastomas.
Clinical
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RB1 (RB Transcriptional Corepressor 1) • KMT2D (Lysine Methyltransferase 2D) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • CCND2 (Cyclin D2)
|
MET amplification • EGFR amplification • PTEN mutation • CDKN2A deletion • MET mutation • PDGFRA mutation • RB1 deletion
1year
Overcoming MET-dependent resistance to selective RET inhibition in patients with RET fusion-positive lung cancer by combining selpercatinib with crizotinib. (PubMed, Clin Cancer Res)
Through the use of SPPs we were able to offer combination therapy targeting MET-amplified resistance identified on the first-in-human study of selpercatinib. These data provide suggest that MET dependence is a recurring and potentially targetable mechanism of resistance to selective RET inhibition in advanced NSCLC.
Clinical • Journal
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
|
MET amplification • RET fusion • MET expression • RET expression • RET positive
|
Xalkori (crizotinib) • Retevmo (selpercatinib)
1year
A phase Ib study of the highly selective MET-TKI savolitinib plus gefitinib in patients with EGFR-mutated, MET-amplified advanced non-small-cell lung cancer. (PubMed, Invest New Drugs)
Savolitinib 600 mg plus gefitinib 250 mg once daily had an acceptable safety profile and demonstrated promising antitumor activity in EGFRm, MET-amplified advanced NSCLC patients who had disease progression on EGFR-TKIs. NCT02374645, Date of registration: March 2nd 2015.
Clinical • P1 data • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M • MET amplification • MET mutation • MET amplification + EGFR mutation • EGFR mutation + EGFR T790M • EGFR T790M negative
|
gefitinib • Orpathys (savolitinib)
over1year
Durable responses to immunotherapy of non-small cell lung cancers harboring MET exon-14-skipping mutation: A series of 6 cases. (PubMed, Lung Cancer)
ICIs could be considered to treat patients whose NSCLCs harbor a METex14 mutation. More biological marker data are needed to identify which patients are most likely to benefit from ICIs.
Clinical • Journal • Tumor Mutational Burden • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • PD-1 (Programmed cell death 1)
|
PD-L1 expression • KRAS mutation • BRAF mutation • MET amplification • MET exon 14 mutation • ALK translocation • EGFR mutation + KRAS mutation • BRAF mutation + MET amplification • TMB + PD-L1 expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Xalkori (crizotinib)
over1year
Phase 1 Study of the Efficacy and Safety of Ramucirumab in Combination with Osimertinib in Advanced T790M-Positive EGFR-Mutant Non-Small Cell Lung Cancer. (PubMed, Clin Cancer Res)
Ramucirumab plus osimertinib demonstrated encouraging safety and antitumor activity in T790M-positive EGFR-mutant NSCLC.
Clinical • P1 data • Journal • Combination therapy
|
EGFR (Epidermal growth factor receptor) • KDR (Kinase insert domain receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • MET amplification • EGFR exon 19 deletion • EGFR amplification • EGFR C797S • EGFR L858R + EGFR T790M • EGFR T790M + exon 19 deletion • EGFR T790M + EGFR C797S • MET amplification + EGFR mutation • EGFR C797S + EGFR T790M + EGFR L858R • EGFR C797S + T790M + exon 19 deletion • EGFR exon 2-7 deletion + EGFR amplification • EGFR mutation + EGFR T790M • EGFR exon 19 deletion + MET amplification • EGFR mutation + EGFR T790M + EGFR C797S • EGFR positive
|
Tagrisso (osimertinib)
over1year
Clinical • Enrollment closed
|
MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • AXL (AXL Receptor Tyrosine Kinase)
|
MET amplification • MET overexpression • RET mutation • RET rearrangement • MET mutation • AXL overexpression
|
Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
over1year
Low-grade BRAF V600E mutant oligodendroglioma-like tumors of children may show EGFR and MET amplification. (PubMed, Brain Pathol)
described a small series of pediatric oligodendroglioma-like tumors with BRAF V600E mutations (3). Interestingly, they exhibited molecular changes usually associated with adult high grade gliomas: chromosome instability, chromosome 7 gains and chromosome 10 loss, but had an indolent natural history.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene)
|
BRAF V600E • BRAF V600 • MET amplification • BRAF mutation + MET amplification
over1year
[VIRTUAL] First-in-human safety, pharmacokinetics, and preliminary efficacy of TPX-0022, a novel inhibitor of MET/SRC/CSF1R in patients with advanced solid tumors harboring genetic alterations in MET (AACR-NCI-EORTC 2020)
TPX-0022 is a novel MET/SRC/CSF1R inhibitor. TPX-0022 was generally well-tolerated. Responses were observed in Δex14 NSCLC and MET amplified GC and CRC.
Clinical • P1 data • PK/PD data • Late-breaking abstract
|
HGF (Hepatocyte growth factor) • CSF1R (Colony stimulating factor 1 receptor)
|
MET amplification • MET exon 14 mutation
|
elzovantinib (TPX-0022)
over1year
[VIRTUAL] Realworld insights into patients (pts) with advanced NSCLC and MET alterations (ESMO Asia 2020)
Screening for these alterations in pts with advanced NSCLC is warranted. Merck KGaA, Darmstadt, Germany.
Clinical • Real-World Evidence • IO biomarker
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
over1year
[VIRTUAL] Real-world insights into patients (pts) with advanced NSCLC and MET alterations (ESMO Asia 2020)
Legal entity responsible for the study: Merck KGaA, Darmstadt, Germany. Funding: Merck KGaA, Darmstadt, Germany.
Clinical • Real-World Evidence • IO biomarker
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
|
Rebif (human IFN-β-1a)
over1year
[VIRTUAL] Realworld insights into patients (pts) with advanced NSCLC and MET alterations (ESMO Asia 2020)
Screening for these alterations in pts with advanced NSCLC is warranted. Merck KGaA, Darmstadt, Germany.
Clinical • Real-World Evidence • IO biomarker
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET exon 14 mutation
over1year
ADVL1622: Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors (clinicaltrials.gov)
P2, N=146, Recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2020 --> Sep 2021 | Trial primary completion date: Sep 2020 --> Sep 2021
Clinical • Trial completion date • Trial primary completion date
|
MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • AXL (AXL Receptor Tyrosine Kinase)
|
MET amplification • MET overexpression • RET mutation • RET rearrangement • MET mutation • AXL overexpression
|
Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
over1year
[VIRTUAL] Liquid Biopsy to Detect MET Alterations in Patients with Advanced NSCLC: Biomarker Analysis from the VISION Study (IASLC-NACLC 2020)
P2 | "Background: In the ongoing, single-arm, Phase II VISION study (NCT02864992), tepotinib (a highly selective MET inhibitor) showed durable clinical activity in NSCLC patients with MET exon 14 skipping... MET exon 14 skipping can be successfully detected through non-invasive liquid biopsy analysis using next-generation sequencing. The rate of MET exon 14 skipping and the genomic profile and demographics of patients were similar to previously reported data. This abstract and presentation was previously presented at AACR 2020."
Clinical • Liquid biopsy
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • GNAS (GNAS Complex Locus)
|
TP53 mutation • EGFR mutation • BRAF mutation • MET amplification • MET exon 14 mutation • ROS1 fusion • MET amplification + EGFR mutation • BRAF mutation + MET amplification • BRAF amplification
|
Guardant360® CDx
|
Tepmetko (tepotinib) • Rebif (human IFN-β-1a)
over1year
[VIRTUAL] INSIGHT 2: Tepotinib + Osimertinib in EGFR-Mutant NSCLC with Resistance to 1st-Line Osimertinib due to MET Amplification (IASLC-NACLC 2020)
Tepotinib + gefitinib is associated with improved outcomes in patients with EGFR-mutant MET-amplified non-small cell lung cancer (NSCLC) and EGFR TKI resistance compared to chemotherapy (INSIGHT: NCT01982955); progression-free survival was 16.6 vs 4.2 months (hazard ratio [HR]=0.13; 90% CI: 0.04, 0.43) and overall survival was 37.3 vs 13.1 months (HR=0.08; 90% CI: 0.01, 0.51)... As this is a trial in progress, results and conclusions cannot be shared yet. Previously presented at ESMO Congress 2020, “FNP:1415TiP”, “Egbert F. Smit et al.” - Reused with permission
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • MET amplification • MET mutation • MET amplification + EGFR mutation
|
Tagrisso (osimertinib) • gefitinib • Tepmetko (tepotinib) • Rebif (human IFN-β-1a)
over1year
Study of Crizotinib for ROS1 and MET Activated Lung Cancer (clinicaltrials.gov)
P2, N=50, Recruiting, University Health Network, Toronto | Not yet recruiting --> Recruiting
Enrollment open
|
MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • MET exon 14 mutation • ROS1 rearrangement • MET mutation
|
Xalkori (crizotinib)
over1year
EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer. (PubMed, Ther Adv Med Oncol)
After controlling for stage of disease at diagnosis, subjects with late-stage disease demonstrated shorter median survival when exhibiting high co-expression of EGFR/c-Met (8.1 month versus 22.3 month, p = 0.050), mTOR (6.7 month versus 22.3 month, p = 0.002), and p-mTOR (8.1 month versus 25.4 month, p = 0.004) compared with low levels. These findings suggest that increased EGFR/c-Met signaling is correlated with upregulated mTOR/S6K signaling, which may in turn be associated with shorter median survival in late-stage NSCLC.
Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
MET amplification • MET expression
over1year
Comparison of Sequential Testing and Next Generation Sequencing in advanced Lung Adenocarcinoma patients - A single centre experience. (PubMed, Lung Cancer)
NGS offered a less expensive and more reliable model of diagnosis respect to sequential one for patients affected by NSCLC-A.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
HER-2 amplification • BRAF mutation • MET amplification • ROS1 rearrangement • MET mutation • BRAF mutation + MET amplification
over1year
Trial of Cabozantinib (XL184) in Non-Small Cell Lung Cancer With Brain Metastases (clinicaltrials.gov)
P2, N=5, Terminated, Liza Villaruz, MD | Completed --> Terminated; Trial stopped due to slow patient accrual.
Clinical • Trial termination
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR L858R • MET amplification • EGFR exon 19 deletion • ALK rearrangement
|
Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)
over1year
Molecular Profiling of Afatinib-Resistant Non-Small Cell Lung Cancer Cells in vivo Derived from Mice. (PubMed, Pharmacol Res)
We established three HCC827 sublines resistant to afatinib (IC > 1 µM) with cross-resistance to gefitinib (IC > 5 µM)...PHA665752, a c-MET inhibitor, remarkably increased the sensitivity of these resistant cells to afatinib (IC = 12-123 nM). We established afatinib-resistant lung cancer cell lines and here report genes associated with afatinib resistance in human NSCLC. These cell lines and the identified genes serve as useful investigational tools, prognostic biomarkers of TKI therapies, and promising molecule targets for development of human NSCLC therapeutics.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • MET amplification
|
Gilotrif (afatinib) • gefitinib • PHA665752
over1year
The METeoric rise of MET in lung cancer. (PubMed, Cancer)
De novo MET amplifications are found in 1% to 5% of NSCLC cases, also predominantly in adenocarcinoma. In the current review, the authors discussed the biology of MET, how to diagnose clinically relevant alterations, and the rising clinical importance of these alterations in light of the emergence of multiple targeted therapies, both within the context of MET as a driver of resistance and in its own right.
Review • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • HGF (Hepatocyte growth factor)
|
MET amplification • MET mutation
over1year
Characterization of MET exon 14 alteration and association with clinical outcomes of crizotinib in Chinese lung cancers. (PubMed, Lung Cancer)
Our study demonstrated a prevalence of 1.1 % for MET-ex14 alterations among the Chinese population. Our study also contributes to a better understanding of molecular factors that are associated with clinical outcomes of patients with MET exon 14 alterations.
Clinical • Clinical data • Journal
|
TP53 (Tumor protein P53)
|
MET amplification • MET exon 14 mutation • MET mutation
|
Xalkori (crizotinib)
over1year
[VIRTUAL] Capmatinib in patients with METex14-mutated or highly MET-amplified advanced non-small cell lung cancer (NSCLC): results from cohort 6 of the phase 2 GEOMETRY mono-1 study (DGHO 2020)
Capmatinib was confirmed to be efficacious in 2nd line, METex14-mutated NSCLC pts. This is the first cohort where capmatinib has been administered without fasting restriction and data confirm the favorable safety profile.
Clinical • P2 data
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
MET amplification • MET exon 14 mutation • MET mutation • ALK translocation
|
Tabrecta (capmatinib)
over1year
[VIRTUAL] EATON: A Phase I Dose Escalation Study of Nazartinib (EGF816) and Trametinib in Patients with EGFR Mutated Non-Small Cell Lung Cancer - Preliminary Data (DGHO 2020)
Treatment with nazartinib 100 mg QD and trametinib 1 mg QD resulted in a DLT in two of six individuals. Thus, three additional patients will be enrolled in a third cohort at the same dose level. Efficacy data are premature and needs further evaluation.
Clinical • P1 data
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification • MET mutation • EGFR mutation + EGFR T790M
|
Mekinist (trametinib) • nazartinib (EGF816)
over1year
[VIRTUAL] EATON: A Phase I Dose Escalation Study of Nazartinib (EGF816) and Trametinib in Patients with EGFR Mutated Non-Small Cell Lung Cancer - Preliminary Data (DGHO 2020)
Treatment with nazartinib 100 mg QD and trametinib 1 mg QD resulted in a DLT in two of six individuals. Thus, three additional patients will be enrolled in a third cohort at the same dose level. Efficacy data are premature and needs further evaluation.
Clinical • P1 data
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification • MET mutation • EGFR mutation + EGFR T790M
|
Mekinist (trametinib) • nazartinib (EGF816)
over1year
[VIRTUAL] Capmatinib in patients with METex14-mutated or highly MET-amplified advanced non-small cell lung cancer (NSCLC): results from cohort 6 of the phase 2 GEOMETRY mono-1 study (DGHO 2020)
Capmatinib was confirmed to be efficacious in 2nd line, METex14-mutated NSCLC pts. This is the first cohort where capmatinib has been administered without fasting restriction and data confirm the favorable safety profile.
Clinical • P2 data
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
MET amplification • MET exon 14 mutation • MET mutation • ALK translocation
|
Tabrecta (capmatinib)
over1year
[VIRTUAL] EATON: A Phase I Dose Escalation Study of Nazartinib (EGF816) and Trametinib in Patients with EGFR Mutated Non-Small Cell Lung Cancer - Preliminary Data (DGHO 2020)
Treatment with nazartinib 100 mg QD and trametinib 1 mg QD resulted in a DLT in two of six individuals. Thus, three additional patients will be enrolled in a third cohort at the same dose level. Efficacy data are premature and needs further evaluation.
Clinical • P1 data
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR T790M • MET amplification • MET mutation • EGFR mutation + EGFR T790M
|
Mekinist (trametinib) • nazartinib (EGF816)
over1year
[VIRTUAL] Capmatinib in patients with METex14-mutated or highly MET-amplified advanced non-small cell lung cancer (NSCLC): results from cohort 6 of the phase 2 GEOMETRY mono-1 study (DGHO 2020)
Capmatinib was confirmed to be efficacious in 2nd line, METex14-mutated NSCLC pts. This is the first cohort where capmatinib has been administered without fasting restriction and data confirm the favorable safety profile.
Clinical • P2 data
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
MET amplification • MET exon 14 mutation • MET mutation • ALK translocation
|
Tabrecta (capmatinib)
over1year
[VIRTUAL] Capmatinib in patients with METex14-mutated or highly MET-amplified advanced non-small cell lung cancer (NSCLC): results from cohort 6 of the phase 2 GEOMETRY mono-1 study (DGHO 2020)
Capmatinib was confirmed to be efficacious in 2nd line, METex14-mutated NSCLC pts. This is the first cohort where capmatinib has been administered without fasting restriction and data confirm the favorable safety profile.
Clinical • P2 data
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
MET amplification • MET exon 14 mutation • MET mutation • ALK translocation
|
Tabrecta (capmatinib)
over1year
Clinical • New P2 trial
|
TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
TP53 mutation • HER-2 amplification • MET amplification • MET mutation • MET N375S
|
Gilotrif (afatinib)