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BIOMARKER:

MET amplification + EGFR mutation

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, EGFR, ERBB, ERBB1, Epidermal growth factor receptor
Entrez ID:
7ms
Brief Report: Clinical Response, Toxicity, and Resistance Mechanisms to Osimertinib Plus MET Inhibitors in Patients With EGFR-Mutant MET-Amplified NSCLC. (PubMed, JTO Clin Res Rep)
Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Dual EGFR and MET inhibition yielded high clinical response rate after progression on OSI. Resistance mechanisms to EGFR-MET double TKI inhibition include MET secondary mutation, EGFR secondary mutation, or loss of MET amplification.
Journal
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EGFR (Epidermal growth factor receptor) • FGFR2 (Fibroblast growth factor receptor 2)
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EGFR mutation • MET amplification • FGFR2 fusion • EGFR C797S • MET amplification + EGFR mutation • EGFR G796S
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Xalkori (crizotinib) • Tagrisso (osimertinib) • Orpathys (savolitinib) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
11ms
Phase 1b study of HS-10241 combined with almonertinib in pre-treated advanced non-small cell lung cancer (NSCLC) harboring EGFR mutation. (ASCO 2023)
HS-10241 in combination with almonertinib was well tolerated, and showed encouraging antitumor activity in treatment of advanced NSCLC with EGFR mutation and MET amplification following prior EGFR-TKI, whether MET GCN ≥10 or MET GCN ≥5 but < 10. Clinical trial information: NCT05430386.
P1 data • Metastases
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • MET amplification • MET mutation • MET amplification + EGFR mutation • EGFR mutation + MET amplification • EGFR mutation + MET-CEP7 fusion
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Ameile (aumolertinib) • HS-10241
over1year
The MET inhibitor ABN401 in combination with the third-generation EGFR-TKI is effective MET-amplified and EGFR-mutant NSCLC with acquired resistance to third-generation EGFR-TKI in preclinical models (ESMO 2022)
Methods The signal transduction inhibition and cytotoxic response of ABN401 in combination with Lazertinib were tested in vitro against Osimertinib-resistance NSCLC cell lines (HCC827-AR) and patient-derived organoid (YUO-010), analyzed by western blot and Cell Titer-Glo assay. Notably, in MET gene amplification (PDX model YHIM-1035, gefitinib/Osimertinib resistant), ABN401 alone showed a potent therapeutic effect. Conclusions Our findings suggest that the clinical application of ABN401 in combination with a third-generation EGFR-TKI to NSCLC patients with MET gene amplification can provide a promising therapeutic strategy for overcoming acquired resistance to EGFR-TKIs.
Preclinical • Combination therapy
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • EGFR exon 19 deletion • MET amplification • EGFR T790M • MET mutation • MET amplification + EGFR mutation
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Tagrisso (osimertinib) • gefitinib • Leclaza (lazertinib) • babamekip (ABN401)
almost3years
[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
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • MET amplification • EGFR exon 20 insertion • HER-2 exon 20 insertion • MET mutation • MET amplification + EGFR mutation • EGFR exon 18 mutation • HER-2 exon 20 mutation
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Gilotrif (afatinib) • lapatinib • Nerlynx (neratinib) • Pozenveo (poziotinib)
3years
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 • MET mutation • MET amplification + EGFR mutation
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gefitinib • Tabrecta (capmatinib)
over3years
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
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • MET amplification • MET mutation • MET amplification + EGFR mutation
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Xalkori (crizotinib) • Imfinzi (durvalumab) • gefitinib • pemetrexed
over3years
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
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • MET amplification • EGFR T790M • MET mutation • MET amplification + EGFR mutation • EGFR T790M negative • EGFR mutation + EGFR T790M
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gefitinib • Orpathys (savolitinib)
over3years
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
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EGFR (Epidermal growth factor receptor) • KDR (Kinase insert domain receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR T790M • EGFR amplification • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • EGFR C797S + EGFR T790M + EGFR exon 19 deletion • EGFR positive • MET amplification + EGFR mutation • EGFR T790M + EGFR C797S • EGFR exon 2-7 deletion + EGFR amplification • EGFR mutation + EGFR T790M • EGFR exon 19 deletion + MET amplification • EGFR mutation + EGFR T790M + EGFR C797S • EGFR T790M + exon 19 deletion
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Tagrisso (osimertinib)
over3years
[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
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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)
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TP53 mutation • EGFR mutation • BRAF mutation • MET amplification • MET exon 14 mutation • ROS1 fusion • MET amplification + EGFR mutation • BRAF mutation + MET amplification • BRAF amplification
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Guardant360® CDx
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Tepmetko (tepotinib)
over3years
[VIRTUAL] INSIGHT 2: Tepotinib + osimertinib in patients (pts) with EGFR-mutant NSCLC having acquired resistance to first-line osimertinib due to MET amplification (METamp) (ESMO 2020)
Tepotinib + gefitinib is associated with improved outcomes in pts with EGFR-mutant METamp NSCLC and EGFR TKI resistance compared to chemotherapy (INSIGHT: NCT01982955); 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). Funding: Merck KGaA, Darmstadt, Germany. Clinical trial identification: NCT03940703.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • MET amplification • MET amplification + EGFR mutation
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Tagrisso (osimertinib) • gefitinib • Tepmetko (tepotinib)
over3years
[VIRTUAL] Disease monitoring and TKI resistance mutations of EGFR mutation-positive NSCLC patients via circulating tumour DNA (ESMO 2020)
One patient had EGFR L858R and T790M mutations and progressed very quickly on erlotinib. While detection of T790M mutation decreased upon osimertinib administration, L858R level stayed the same...Legal entity responsible for the study: Roche Sequencing Solutions, Inc. Funding: Roche Sequencing Solutions, Inc.
Clinical
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53)
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TP53 mutation • EGFR mutation • EGFR L858R • MET amplification • EGFR T790M • KIT mutation • EGFR L858R + EGFR T790M • MET amplification + EGFR mutation • EGFR mutation + EGFR T790M
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Tagrisso (osimertinib) • erlotinib