News - MET amplification

A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer. (PubMed, J Gastrointest Cancer)

Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.

9 days ago

P2 data • Journal • Metastases

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • RAS wild-type

Orpathys (savolitinib)

15d

Adenocarcinoma of the rete testis: clinicopathological study of 18 cases with emphasis on MET amplification and a review of the literature. (PubMed, Histopathology)

Primary ACRT is a rare malignant tumour which poses a diagnostic challenge, and is associated with poor prognosis. Cases of ACRT with MET amplification might represent promising candidates for the treatment with MET inhibitors.

15 days ago

Review • Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • WT1 (WT1 Transcription Factor) • PAX8 (Paired box 8)

MET amplification

15d

A universal immunohistochemistry analyzer for generalizing AI-driven assessment of immunohistochemistry across immunostains and cancer types. (PubMed, NPJ Precis Oncol)

In a discovery application, the UIHC model assigned higher tumor proportion scores to MET amplification cases, but not MET exon 14 splicing or other non-small cell lung cancer cases. This UIHC model represents a novel role for DL that further advances quantitative analysis of IHC.

15 days ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET exon 14 mutation

15d

Evolution of Rapid Clonal Dynamics and Non-Cross-Resistance in Response to Alternating Targeted Therapy and Chemotherapy in BRAF-V600E-Mutant Colon Cancer. (PubMed, JCO Precis Oncol)

These findings suggest rational strategies for combining sequential chemotherapy and BRAF-/EGFR-directed therapy in BRAF-V600E-mutant colon cancer to prevent resistance and improve outcome. The data demonstrate rapid clonal dynamics in response to effective therapies in BRAF-V600E-mutant colon cancer that can be monitored by serial cfDNA analysis. Moreover, in mismatch repair-proficient BRAF-V600E-mutant colon cancers, combined EGFR and BRAF/MEK therapy is not cross-resistant with standard chemotherapy, suggesting new rational combination treatment strategies.

15 days ago

Journal

BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)

BRAF V600E • EGFR mutation • BRAF V600 • MET amplification

20d

Geometry-N: Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC (clinicaltrials.gov)

P2, N=4, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; The study was terminated early due to recruitment challenges.

20 days ago

Trial termination

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET exon 14 mutation • MET mutation

Tabrecta (capmatinib)

24d

Research progress on the role of bypass activation mechanisms in resistance to tyrosine kinase inhibitors in non-small cell lung cancer. (PubMed, Front Oncol)

Some clinical trials based on this combined treatment approach have yielded promising preliminary results, offering more treatment options for NSCLC patients with TKI resistance. Additionally, early identification of resistance mechanisms through liquid biopsy, personalized targeted therapy against these mechanisms, and preemptive targeting of drug-tolerant persistent cells may provide NSCLC patients with more sustained and effective treatment.

24 days ago

Review • Journal

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • AXL (AXL Receptor Tyrosine Kinase)

MET amplification • EGFR amplification

24d

Expression of SPRED2 in the lung adenocarcinoma. (PubMed, Pathol Res Pract)

In vitro, SPRED2 deletion increased cell proliferation, migration and invasion of three LUAD cell lines (A549:KRAS mutation, H1993:METamplification, and HCC4006:EGFR mutation), whereas SPRED2 overexpression decreased these responses. Thus, SPRED2 appears to be a regulator of LUAD progression and a potential target for the treatment of LUAD.

24 days ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • SPRED2 (Sprouty Related EVH1 Domain Containing 2)

KRAS mutation • EGFR mutation • MET amplification • SPRED2 deletion

A Study to Assess Disease Activity of Intravenously (IV) Infused Telisotuzumab Vedotin in Adult Participants With Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)

P2, N=9, Terminated, AbbVie | Trial completion date: Mar 2026 --> Oct 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2025 --> Oct 2024; Strategic considerations

1 month ago

Trial completion date • Trial termination • Trial primary completion date • Metastases

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification

telisotuzumab vedotin (ABBV-399)

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

1 month ago

Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion

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Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

Impact of genomic alterations measured in circulating tumor DNA (ctDNA) on clinical response to telisotuzumab vedotin treatment in patients with non-small cell lung cancer (NSCLC) (AIOM 2024)

METamp occurred more frequently in responders; but Teliso-V activity wasn’t restricted to these pts: most responders weren’t METamplified. Specific genomic alts beyond MET may influence clinical response. The current analysis demonstrated numeric differences between pts with identified drivers who did or didn’t respond to Teliso-V.

1 month ago

Clinical • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase)

KRAS G12C • MET amplification • KRAS G12

Labcorp® Plasma Complete™

telisotuzumab vedotin (ABBV-399)

MET amplification correlates with poor prognosis and immunotherapy response as a subtype of melanoma: a multicenter retrospective study. (PubMed, BMC Cancer)

This database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.

1 month ago

Retrospective data • Journal • IO biomarker

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification

MSK-IMPACT

Erratum: Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. (PubMed, J Clin Oncol)

No abstract available

1 month ago

Journal

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • MET amplification

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Profiles, and Preliminary Efficacy of SYS6023 in Patients with Advanced Solid Tumors (ChiCTR2400089836)

P1, N=388, Recruiting, Shanghai Chest Hospital; CSPC Megalith Biopharmaceutical Co., Ltd

1 month ago

New P1 trial • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • HER-2 negative • BRAF V600 • HER-2 expression • ALK positive • MET amplification • ALK fusion • ERBB3 expression • RET mutation • ROS1 fusion • MET mutation • NRG1 fusion • RET rearrangement • KRAS G12 • KRAS amplification • ER expression • PGR expression • ALK-ROS1 fusion • NRG1 fusion • NTRK fusion

Fusion transcriptome landscape in Glioblastoma (SNO 2024)

Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.

1 month ago

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) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)

TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion

MI Tumor Seek™

The potential role of next-generation sequencing in identifying MET amplification and disclosing resistance mechanisms in NSCLC patients with osimertinib resistance. (PubMed, Front Oncol)

The known resistance mechanisms, including MET amplification, EGFR (C797S, L718Q/R), TP53, CDK4, CDK6, CDKN2A, BRAF, KRAS, NRAS and PIK3CA mutations were also disclosed in our cohort. NGS assay can achieve a high concordance with FISH in MET amplification detection and has advantages in portraying various genetic alterations, which is of worthy in clinical promotion.

1 month ago

Journal • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • 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) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)

TP53 mutation • EGFR mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • MET amplification • EGFR T790M • EGFR C797S • EGFR L718Q • BRAF amplification • EGFR C797S + MET amplification

Tagrisso (osimertinib)

Comprehensive liquid biopsy analysis for monitoring NSCLC patients under second-line osimertinib treatment. (PubMed, Front Oncol)

AXL and PIM-1 expression detected in CTCs during treatment suggesting new possible therapeutic strategies. Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs.

1 month ago

Journal • Liquid biopsy • PD(L)-1 Biomarker • IO biomarker • Biopsy

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • AXL (AXL Receptor Tyrosine Kinase) • B2M (Beta-2-microglobulin) • FOXA1 (Forkhead Box A1) • PIM1 (Pim-1 Proto-Oncogene) • VIM (Vimentin) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • KRT19 (Keratin 19) • RASSF1 (Ras Association Domain Family Member 1) • WIF1 (WNT Inhibitory Factor 1) • BRMS1 (BRMS1 Transcriptional Repressor And Anoikis Regulator)

PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • MET amplification • EGFR T790M • MET mutation • KRAS G12 • EGFR mutation + PIK3CA mutation • HER-2 amplification + PD-L1 expression • VIM expression • HER-2 amplification + MET amplification • RASSF1 methylation

Tagrisso (osimertinib)

Tepotinib in Cholangiocarcinoma with MET Amplification: A Case Report. (PubMed, Onco Targets Ther)

Systemic therapy, such as chemotherapy using gemcitabine and cisplatin, is the first choice for patients with cholangiocarcinoma who were inoperable. The development of precision medicine has expanded the paradigm of targeted therapies to increasingly favorable options in the second line and beyond, and prolong overall survival. Detecting druggable mutations (mutations potentially amenable to treatment with) for identifying a landscape of therapeutic options is imperative for managing cholangiocarcinoma.

1 month ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification

cisplatin • gemcitabine • Tepmetko (tepotinib)

KisMET-01: Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer (clinicaltrials.gov)

P1, N=250, Recruiting, Mythic Therapeutics | N=150 --> 250

1 month ago

Enrollment change

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET exon 14 mutation • MET mutation

MYTX-011

2ms

LUNG-MAP SUB-STUDY: Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has Increased Copies of the MET Gene (An Expanded Lung-MAP Treatment Trial) (clinicaltrials.gov)

P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

2 months ago

Enrollment open • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • 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)

BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • HER-2 mutation • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • RET rearrangement

Rybrevant (amivantamab-vmjw)

2ms

Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer. (PubMed, J Hepatol)

Among patients with advanced BTC, ctDNA-based genotyping showed acceptable concordance with tissue genomic profiling. Liquid biopsy using ctDNA could be a valuable complement to tissue-based genomic analysis in BTC.

2 months ago

Journal • BRCA Biomarker • Circulating tumor DNA • Metastases • Discordant

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

BRCA2 mutation • BRCA1 mutation • HER-2 amplification • PIK3CA mutation • IDH1 mutation • MET amplification • FGFR2 mutation • FGFR2 fusion • MET mutation • PIK3CA amplification

AlphaLiquid® 100

cisplatin • gemcitabine

2ms

ALK-tyrosine kinase inhibitor intrinsic resistance due to de novo MET-amplification in metastatic ALK-rearranged non-small cell lung cancer effectively treated by alectinib-crizotinib combination-case report. (PubMed, Transl Lung Cancer Res)

A 43-year-old, female diagnosed with T4N3M1c NSCLC harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variant 1 (EML4-ALK v.1) and TP53 co-mutation, displayed only mixed response after three months and highly symptomatic progression after 6 months of first-line brigatinib treatment. The latter may represent a mechanism of intrinsic ALK-TKI resistance and its recognition by FISH, in NGS-negative cases, may be considered before initiating first-line treatment. This recognition is clinically important as combined therapy with ALK-TKI and MET-inhibitor should be the preferred first-line treatment.

2 months ago

Journal • Metastases

ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4)

TP53 mutation • MET amplification • ALK rearrangement • MET overexpression • ALK fusion • MET expression

Xalkori (crizotinib) • Alecensa (alectinib) • Alunbrig (brigatinib)

2ms

Exploration of efficacy of the first-line treatment for advanced non-small cell lung cancer with primary MET-amplification: Retrospective evaluation of 36 cases. (PubMed, Int Immunopharmacol)

Immuno-chemotherapy is a first-line optional treatment strategy in addition to targeted therapy for NSCLC patients with primary METamp. Foxp3-negative expression better predicts the near-term efficacy of immunotherapy.

2 months ago

Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases

PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase) • PD-1 (Programmed cell death 1) • FOXP3 (Forkhead Box P3)

PD-L1 expression • MET amplification • PD-L1 negative • FOXP3 expression

2ms

NRG-LU003: Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer (clinicaltrials.gov)

P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

2 months ago

Trial completion date

MET (MET proto-oncogene, receptor tyrosine kinase)

ALK positive • MET amplification • ALK rearrangement

cisplatin • Xalkori (crizotinib) • carboplatin • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • pemetrexed • Alunbrig (brigatinib) • Ensacove (ensartinib)

2ms

SOUND: Savolitinib Combine With Durvalumab in EGFR Wild-type Locally Advanced or Metastatic NSCLC (clinicaltrials.gov)

P2, N=47, Active, not recruiting, AstraZeneca | Suspended --> Active, not recruiting | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Oct 2024 --> Aug 2025

2 months ago

Enrollment closed • Trial completion date • Trial primary completion date • Metastases

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • EGFR wild-type • MET exon 14 mutation • MET overexpression • MET mutation

Imfinzi (durvalumab) • Orpathys (savolitinib)

2ms

A Master Protocol to Evaluate Biomarker-Driven Therapies and Immunotherapies in Previously-Treated Non-Small Cell Lung Cancer (Lung-MAP Screening Study) (SWOG-Fall 2024)

Current sub-studies: S1900E (KRAS) activated on April 2, 2021 and is studying sotorasib (AMG 510) in non-squamous NSCLC...S1900G (EGFR and MET) activated on April 3, 2023 and is studying capmatinib and osimertinib with or without ramucirumab in NSCLC. S1900K (MET exon 14 skipping) activated on December 18, 2023 and is studying tepotinib with or without ramucirumab in NSCLC. S1900J (MET amplification) is opening fall 2024 and is studying amivantamab in NSCLC...One hundred seventy-four (5%) were submitted with the classification of "Other". The most common reasons included: no sub-studies available, patient chose hospice, and patient transferred to different hospital.

2 months ago

Clinical • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

BRAF V600E • EGFR mutation • BRAF V600 • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion

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Tagrisso (osimertinib) • Lumakras (sotorasib) • Cyramza (ramucirumab) • Rybrevant (amivantamab-vmjw) • Tepmetko (tepotinib) • Tabrecta (capmatinib)

2ms

Use of Oncogene Overlap by Tissue-Based Next-Generation Sequencing to Explore the Mutational Landscape and Survival Impact of HER2, KRAS and MET Copy-Number Gain in Nonsmall Cell Lung Cancer. (PubMed, Clin Lung Cancer)

Tissue NGS-based HER2, KRAS and MET CNG thresholds set by oncogene overlap identified potentially clinically relevant "Amp" subgroups with altered genetic profiles and decreased survival. Prospective research into targeted therapy benefit in these groups is encouraged.

2 months ago

Journal • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)

KRAS mutation • EGFR mutation • BRAF mutation • HER-2 amplification • HER-2 negative • MET amplification • MET mutation • BRAF mutation + EGFR mutation

2ms

A Phase I Study of SCC244 in Patients With Advanced MET Alterations Solid Tumors (clinicaltrials.gov)

P1, N=177, Completed, Haihe Biopharma Co., Ltd. | Unknown status --> Completed | N=75 --> 177

2 months ago

Trial completion • Enrollment change • Metastases

MET amplification • MET overexpression • MET expression

Haiyitan (gumarontinib)

2ms

Study to Evaluate the Safety and Anti-tumor Activity of SCC244 (clinicaltrials.gov)

P1, N=56, Completed, Haihe Biopharma Co., Ltd. | Unknown status --> Completed | N=113 --> 56

2 months ago

Trial completion • Enrollment change • Metastases

KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

EGFR mutation • MET amplification • MET exon 14 mutation • MET overexpression • ALK mutation • MET mutation • ROS1 wild-type

Haiyitan (gumarontinib)

2ms

Response to Crizotinib After Entrectinib Resistance in ROS1-Rearranged, MET-Amplified Lung Adenocarcinoma. (PubMed, JCO Precis Oncol)

Crizotinib successfully overcomes MET amplification in ROS1-rearranged NSCLC after entrectinib failure.

2 months ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

MET amplification • ROS1 rearrangement • ROS1 amplification

Xalkori (crizotinib) • Rozlytrek (entrectinib)

2ms

Advancements in fourth-generation EGFR TKIs in EGFR-mutant NSCLC: Bridging biological insights and therapeutic development. (PubMed, Cancer Treat Rev)

Nevertheless, disease progression inevitably occurs, limiting osimertinib long-term efficacy...Early phase 1/2 clinical trials are ongoing to elucidate their activity also in the clinical setting. Aim of this review is to provide a state-of-the-art analysis on preclinical development of fourth-generation EGFR-TKIs and promising preliminary clinical data.

2 months ago

Review • Journal

HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • HER-2 amplification • HER-2 mutation • MET amplification • EGFR C797S

Tagrisso (osimertinib)

3ms

Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial. (PubMed, Lancet Oncol)

These long-term results support METex14 as a targetable oncogenic driver in NSCLC and add to the evidence supporting capmatinib as a targeted treatment option for treatment-naive and previously treated patients with METex14 NSCLC.

3 months ago

P2 data • Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • ALK rearrangement • EGFR wild-type • MET exon 14 mutation • MET mutation

Tabrecta (capmatinib)

3ms

Exceptional sustained long-term complete response to Tepotinib in a MET-amplified advanced intrahepatic biliary tract cancer failing Durvalumab plus Cisplatin and Gemcitabine. (PubMed, Oncologist)

Tepotinib showed remarkable efficacy in treating MET-amplified intrahepatic cholangiocarcinoma, underscoring the importance of molecular profiling in BTCs and suggesting a potential new therapeutic approach for this rare cancer subtype.

3 months ago

Journal • PD(L)-1 Biomarker • Metastases

TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)

TP53 mutation • MET amplification • MET mutation

cisplatin • Imfinzi (durvalumab) • gemcitabine • Tepmetko (tepotinib)

3ms

Registry of Genetic Alterations of Taiwan Non-Small Cell Lung Cancer by Comprehensive Next-Generation Sequencing: A Real-World Cohort Study-Taiwan Cooperative Oncology Group T1521. (PubMed, JCO Glob Oncol)

This multicenter registration study investigated tissue-based NGS for a specific patient population with NSCLC in Taiwan.

3 months ago

Real-world evidence • Journal • Next-generation sequencing • Real-world

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • ALK positive • MET amplification • RET fusion • ALK rearrangement • MET exon 14 mutation • EGFR C797S • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • ALK negative

ACTOnco

Tagrisso (osimertinib)

3ms

Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial. (PubMed, Nat Med)

The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. These findings support treatment with Enco+Cetux±Bini for patients with BRAF-V600E-mutant mCRC and provide insights into the biology of response and resistance to MAPK-pathway-targeted therapy. ClinicalTrials.gov registration: NCT02928224.

3 months ago

P3 data • Journal • Metastases

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

TP53 mutation • BRAF V600E • BRAF V600 • MET amplification • MET mutation

Erbitux (cetuximab) • Mektovi (binimetinib) • Braftovi (encorafenib)

3ms

EGFR plus MET targeted therapies for overcoming treatment resistance in EGFR mutant NSCLC. A Case Report. (PubMed, Oncol Res Treat)

The molecular heterogeneity of this condition has significantly increased in complexity over recent years, marked by the identification of baseline co-alterations and development of a broad spectrum of resistance mechanisms post-EGFR tyrosine kinase inhibitor (TKI) therapy. This complexity poses a substantial challenge to clinicians. Despite the rapid advancement of targeted therapies and the implementation of treatment escalation through combination strategies, there remains an ongoing debate regarding which patients would benefit most from combination therapies, both in the initial treatment phase and in the setting of disease progression, particularly when off-target resistance mechanisms or co-alterations are identified.

3 months ago

Journal

EGFR (Epidermal growth factor receptor)

EGFR mutation • MET amplification

3ms

Ph2 Study of Savolitinib and Durvalumab (MEDI4736) Combination in Advanced MET Amplified Gastric Cancer(VIKTORY-2) (clinicaltrials.gov)

P2, N=25, Recruiting, Jeeyun Lee | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

3 months ago

Trial completion date • Trial primary completion date • Metastases

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification

Imfinzi (durvalumab) • Orpathys (savolitinib)

3ms

A phase Ib/II study of the highly selective MET-TKI Vebreltinib plus Tislelizumab Injection with or without Platinum-based Doublet Chemotherapy in patients with MET-amplified and PD-L1-positive Locally advanced or metastatic non-small-cell lung cancer (ChiCTR2400088382)

P1/2, N=68, Not yet recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

3 months ago

New P1/2 trial • Metastases

PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase)

PD-L1 expression • EGFR mutation • MET amplification • EGFR wild-type • RAS wild-type

Tevimbra (tislelizumab-jsgr) • bozitinib (APL-101)

3ms

A Single-arm, Multicenter, Phase Il clinical Study of Platinum-based Doublet Chemotherapy Sequential Vebreltinib as adjuvant Therapy for Patients With Resectable, stage IB-IIIB(N2) Non-Small Cell Lung Cancer with c-MET Exon 14 skipping mutation with or without other MET Alterations (ChiCTR2400085552)

P4, N=20, Recruiting, The First Affiliated Hospital, Zhejiang University School of Medicine; The First Affiliated Hospital, Zhejiang University School of Medicine | Not yet recruiting --> Recruiting

3 months ago

Enrollment open

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET overexpression

gemcitabine • pemetrexed • bozitinib (APL-101)

3ms

R5093-ONC-1863: A Study of REGN5093 in Adult Patients With Mesenchymal Epithelial Transition Factor (MET)-Altered Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)

P1/2, N=231, Active, not recruiting, Regeneron Pharmaceuticals | N=82 --> 231 | Trial completion date: Oct 2024 --> Jan 2032 | Trial primary completion date: Oct 2024 --> Jan 2032

3 months ago

Enrollment change • Trial completion date • Trial primary completion date • Metastases

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET exon 14 mutation • MET mutation • MET expression • MET elevation

davutamig (REGN5093)

5ms

Intrinsic ALK-TKI Resistance Due to Met-Coamplification in ALK+ NSCLC, Effectively Treated by Alectinib-crizotinib Combination (IASLC-WCLC 2024)

Yet, to our knowledge, we present herein the first case of ALK + NSCLC rapidly progressing on 1 st line Brigatinib treatment due to de novo MET- amplification. The recognition of this mechanism of ALK-TKI resistance by FISH, especially in NGS-negative cases, should be considered before initiating 1 st line treatment. This is of clinical importance, as effective combined therapy with ALK-TKI and MET-inhibitor is feasible.

5 months ago

ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4)

TP53 mutation • MET amplification • ALK rearrangement • MET overexpression • EML4-ALK fusion • ALK fusion • MET expression • ALK amplification • TP53 G245S

Oncomine™ Comprehensive Assay v3M • Archer® FusionPlex® Lung Kit • FusionPlex® Dx

Xalkori (crizotinib) • Alecensa (alectinib) • Alunbrig (brigatinib)

5ms

Analysis of Uncommon EGFR Exon 19 Alterations Identified by Liquid Biopsy in Advanced Non-Small Cell Lung Cancer (NSCLC) (IASLC-WCLC 2024)

Conclusions : To our knowledge, this is the largest liquid biopsy analysis comparing common/uncommon ex19dels in NSCLC and shows similar genomic findings across groups. Further work should be done to explore additional genomic and non-genomic factors to aid in patient selection for EGFR TKIs for uncommon findings.

5 months ago

Liquid biopsy • Metastases • Biopsy

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • 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) • FGFR2 (Fibroblast growth factor receptor 2)

EGFR exon 19 deletion • MET amplification • EGFR T790M • FGFR2 fusion • EGFR C797S • EGFR G724S • EGFR L747_A750delinsP • BRAF amplification • EGFR L747_P753delinsS

Guardant360® CDx

5ms

Mechanisms of resistance to selpercatinib in RET activated NSCLC and MTC from the LIBRETTO-001 trial (ESMO 2024)

P1/2 | "Acquired MoR was identified in 45% of liquid biopsies in the largest prospective dataset studying MoR to RET inhibition. On-target MoR including RET SF G810 muts were more common in MTC than NSCLC. Bypass MoR (30%) included RAS/RAF activating and potentially targetable MET amps."

5 months ago

BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)

MET amplification • RET mutation • BRAF amplification • RET V804*

Guardant360® CDx

Retevmo (selpercatinib)