# MET exon 14 and MET-amplified non-small-cell lung cancer

Source: https://onco.cc/cancers/met-altered-nsclc/  
OnCo record `met-altered-nsclc` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

MET-driven lung cancer comes in three forms: an exon 14 skipping mutation treated with the pills capmatinib or tepotinib, MET amplification that often arises as an escape route from EGFR drugs, and high c-Met protein levels that the antibody-drug conjugate telisotuzumab vedotin targets.

## Summary

MET exon 14 skipping mutations remove the domain that marks the receptor for degradation, so it accumulates and signals persistently; they were shown to be targetable in 2015 when patients responded to crizotinib. Capmatinib (GEOMETRY mono-1, 2020) produced response rates of 68 percent in treatment-naive and 41 percent in previously treated patients and received accelerated approval in May 2020, and tepotinib (VISION, 2020) a 46 percent response rate with approval in February 2021; both are brain-penetrant and cause peripheral oedema. Savolitinib is approved in China for the same mutation, including sarcomatoid tumours. Checkpoint inhibitors work poorly despite frequent PD-L1 expression, and exon 14 patients who are fit and untreated are usually given the MET inhibitor first.

MET amplification behaves differently by context. De novo high-level amplification (gene copy number 10 or more) responds to capmatinib in about a third of patients; low-level amplification does not. As acquired resistance to osimertinib, MET amplification is treated by adding a MET inhibitor to osimertinib: the SAVANNAH and SACHI trials of osimertinib plus savolitinib showed high response rates in patients selected by MET testing, and SACHI led to approval of the combination in China in 2025. Amivantamab, the EGFR-MET bispecific antibody, covers MET-mediated resistance in EGFR-mutated disease as well.

c-Met protein overexpression without a MET genomic alteration is the target of telisotuzumab vedotin, an antibody-drug conjugate with a microtubule payload: LUMINOSITY reported a 35 percent response rate in non-squamous EGFR wild-type tumours with high c-Met expression, and the drug received accelerated approval in May 2025, with TeliMET NSCLC-01 comparing it with docetaxel. Open questions are the best MET inhibitor sequence, whether MET inhibitors should be combined with chemotherapy or immunotherapy first line, and how to define MET amplification consistently across assays.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: MET exon 14 skipping lung cancer; METex14 NSCLC; MET-amplified lung cancer; c-Met overexpressing NSCLC
- Tags: subtype-page; lung
- Group: lung
- Burden: MET exon 14 skipping mutations occur in 3 to 4 percent of non-small-cell lung cancers, typically in older patients and enriched in sarcomatoid tumours; de novo high-level MET amplification in 1 to 2 percent; and MET amplification appears as a resistance mechanism in about 15 percent of EGFR-mutated cancers after osimertinib. About a quarter of non-squamous lung cancers overexpress the c-Met protein.
- Subtypes: MET exon 14 skipping adenocarcinoma or sarcomatoid carcinoma (capmatinib, tepotinib); De novo high-level MET amplification (gene copy number 10 or more); MET amplification as acquired resistance in EGFR-mutated adenocarcinoma (osimertinib plus savolitinib, amivantamab); c-Met protein overexpression without a genomic alteration (telisotuzumab vedotin)
- Biomarkers: MET exon 14 skipping by RNA or DNA sequencing (DNA panels miss some intronic variants); MET gene copy number by fluorescence in situ hybridisation or sequencing; c-Met immunohistochemistry (3+ in 50 percent or more of cells for telisotuzumab vedotin); MET amplification in plasma or tissue at progression on osimertinib; Peripheral oedema and creatinine on MET inhibitors

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/met-altered-nsclc/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/met-altered-nsclc/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/met-altered-nsclc/#what-it-is [4 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/met-altered-nsclc/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/met-altered-nsclc/#treating-it [3 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/met-altered-nsclc/#evidence [27 trials, 3 key papers, 5 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/met-altered-nsclc/#science [4 targets, 2 pathways]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/met-altered-nsclc/where-you-are/ [34 UK centres]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/met-altered-nsclc/#living-with-it [18 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/met-altered-nsclc/coming/ [12 medicines, 26 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/met-altered-nsclc/data/ [74 connected records]

## Standard of care

- Advanced MET exon 14, first line or later: Capmatinib (GEOMETRY mono-1) or tepotinib (VISION); platinum-pemetrexed with or without pembrolizumab if the inhibitor is not tolerated or after it. ([Capmatinib](https://onco.cc/drugs/capmatinib/), [GEOMETRY mono-1](https://onco.cc/trials/geometry-mono-1/), [Tepotinib](https://onco.cc/drugs/tepotinib/), [VISION (tepotinib)](https://onco.cc/trials/nct02864992/), [Capmatinib & tepotinib](https://onco.cc/drugs/capmatinib-tepotinib/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Carboplatin](https://onco.cc/drugs/carboplatin/))
- MET amplification after osimertinib in EGFR-mutated disease: Osimertinib plus savolitinib (SAVANNAH, SACHI) where available; amivantamab plus chemotherapy; platinum-pemetrexed. ([Osimertinib](https://onco.cc/drugs/osimertinib/), [Savolitinib](https://onco.cc/drugs/savolitinib/), [Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib](https://onco.cc/trials/nct03778229/), [Amivantamab](https://onco.cc/drugs/amivantamab/), [A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure](https://onco.cc/trials/nct04988295/), [MET amplification (bypass resistance)](https://onco.cc/terms/met-amplification/))
- c-Met overexpression, previously treated non-squamous: Telisotuzumab vedotin (LUMINOSITY) after platinum chemotherapy; TeliMET NSCLC-01 versus docetaxel is confirmatory. ([Telisotuzumab vedotin](https://onco.cc/drugs/telisotuzumab-vedotin/), [LUMINOSITY](https://onco.cc/trials/luminosity/), [TeliMET NSCLC-01](https://onco.cc/trials/telimet-nsclc-01/), [Docetaxel](https://onco.cc/drugs/docetaxel/))

## State of the art

- Two approved brain-penetrant MET inhibitors for exon 14 skipping with response rates of 40 to 70 percent.
- Osimertinib plus savolitinib for MET-amplified resistance in EGFR-mutated disease (SACHI, approved in China).
- Telisotuzumab vedotin, the first antibody-drug conjugate for a lung cancer selected by protein expression, approved in 2025.

## Open problems

- MET amplification has no agreed threshold and results differ between assays.
- Peripheral oedema limits the dose of every MET inhibitor and has no good treatment.
- Whether MET inhibitors should be combined with chemotherapy or immunotherapy first line in exon 14 disease is untested.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/C-Met
- Wikipedia: https://en.wikipedia.org/wiki/C-Met
- NCCN Guidelines: Non-Small Cell Lung Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450

## Connected records

- cancers: [Adenocarcinoma of the lung](https://onco.cc/cancers/lung-adenocarcinoma/), [ALK-positive non-small-cell lung cancer](https://onco.cc/cancers/alk-positive-nsclc/), [BRAF V600E-mutant non-small-cell lung cancer](https://onco.cc/cancers/braf-v600e-nsclc/), [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [HER2-mutant non-small-cell lung cancer](https://onco.cc/cancers/her2-mutant-nsclc/), [KRAS G12C-mutant non-small-cell lung cancer](https://onco.cc/cancers/kras-g12c-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [NTRK fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ntrk-fusion-nsclc/), [RET fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ret-fusion-nsclc/), [ROS1-positive non-small-cell lung cancer](https://onco.cc/cancers/ros1-positive-nsclc/), [Sarcomatoid carcinoma of the lung](https://onco.cc/cancers/pulmonary-sarcomatoid-carcinoma/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [MET](https://onco.cc/targets/met/)
- drugs: [Amivantamab](https://onco.cc/drugs/amivantamab/), [Capmatinib](https://onco.cc/drugs/capmatinib/), [Capmatinib & tepotinib](https://onco.cc/drugs/capmatinib-tepotinib/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Crizotinib](https://onco.cc/drugs/crizotinib/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Savolitinib](https://onco.cc/drugs/savolitinib/), [Telisotuzumab adizutecan](https://onco.cc/drugs/telisotuzumab-adizutecan/), [Telisotuzumab vedotin](https://onco.cc/drugs/telisotuzumab-vedotin/), [Tepotinib](https://onco.cc/drugs/tepotinib/)
- companies: [AbbVie (incl. ImmunoGen, Capstan)](https://onco.cc/companies/abbvie/), [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Jiangsu Hengrui Pharmaceuticals](https://onco.cc/companies/hengrui/), [Merck KGaA (EMD Serono)](https://onco.cc/companies/merck-kgaa/), [Novartis](https://onco.cc/companies/novartis/)
- pathways: [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [MET amplification (bypass resistance)](https://onco.cc/terms/met-amplification/), [MET exon 14 skipping mutation](https://onco.cc/terms/met-exon-14-skipping/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- trials: [A Confirmatory Clinical Study in NSCLC Patients With MET Exon 14 Mutation (KUNPENG-2)](https://onco.cc/trials/nct05989542/), [A First-in-Human Study of CKD-703 in Advanced Solid Tumors and Non-Small Cell Lung Cancer](https://onco.cc/trials/nct07439094/), [A Phase Ⅱ Study of RC108 in Combination With Furmonertinib for the First-line Treatment of EGFR-Mutated Combined MET-Positive Unresectable Locally Adv](https://onco.cc/trials/nct06962865/), [A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLC](https://onco.cc/trials/nct04606771/), [A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure](https://onco.cc/trials/nct04988295/), [A Study of REGN5093 in Adult Patients With Mesenchymal Epithelial Transition Factor (MET)-Altered Advanced Non-Small Cell Lung Cancer](https://onco.cc/trials/nct04077099/), [A Study of Vebreltinib and Platinum-Containing Double Agents in Subjects With MET-Positive](https://onco.cc/trials/nct06930794/), [A Study to Assess Adverse Events and How Intravenously (IV) Infused Telisotuzumab Vedotin (ABBV-399) Moves Through the Body as a Monotherapy in Adult ](https://onco.cc/trials/nct06568939/), [A Study to Assess Intravenous (IV) Telisotuzumab Adizutecan Compared to Standard of Care in Adult Participants Previously Treated, EGFR Wildtype, Locally Advanc](https://onco.cc/trials/nct07821684/), [A Study to Evaluate the Efficacy and Safety of Glumetinib Combined With Osimertinib Mesylate Versus Platinum-based Doublet Chemotherapy in N](https://onco.cc/trials/nct06829459/), [A Study to Evaluate the Efficacy and Safety of the Combination of Glumetinib and Docetaxel（Albumin Bound）Verse Docetaxel for the Treatment of MET-overexpressed](https://onco.cc/trials/nct06525350/), [ASKC202 Combined With Limertinib Versus Platinum-based Chemotherapy in Treatment of Locally Advanced or Metastatic NSCLC With MET Amplification/Overexpression After Failure of EGFR-TKI Therapy](https://onco.cc/trials/nct07109531/), [Assessment of Anti-tumor and Safety in Glumetinib in Patients With c-MET-positive Non-Small Cell Lung Cancer](https://onco.cc/trials/nct04270591/), [Clinical Study on Savolitinib + Osimertinib in Treatment of EGFRm+/MET+ Locally Advanced or Metastatic NSCLC](https://onco.cc/trials/nct05009836/), [GEOMETRY mono-1](https://onco.cc/trials/geometry-mono-1/), [Glumetinib Combined With Osimertinib Treatment for Non-Small Cell Lung Cancer Patients](https://onco.cc/trials/nct06908772/), [LUMINOSITY](https://onco.cc/trials/luminosity/), [Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib](https://onco.cc/trials/nct03778229/), [Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment](https://onco.cc/trials/nct05261399/), [Study of MCLA-129 in the Treatment of Advanced Non-small Cell Lung Cancer with AGA and MET Amplification.](https://onco.cc/trials/nct06885840/), [TeliMET NSCLC-01](https://onco.cc/trials/telimet-nsclc-01/), [Telisotuzumab Vedotin and Osimertinib for the Treatment of Progressive, Incurable, Non Small Cell Lung Cancer](https://onco.cc/trials/nct07323641/), [Tepotinib vs Standard Treatment in Patients With Advanced MET Exon 14 Mutated Non-Small Cell Lung Cancer Previously Treated](https://onco.cc/trials/nct06908993/), [Vebreltinib Plus PLB1004 as the First-line Therapy for Patients With EGFRm+/MET+ Locally Advanced or Metastatic NSCLC.](https://onco.cc/trials/nct06574347/), [Vebreltinib Plus PLB1004 in EGFR-mutated, Advanced NSCLC With MET Amplification or MET Overexpression Following EGFR-TKI](https://onco.cc/trials/nct06343064/), [Vebreltinib Plus PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFRm, MET+, Locally Advanced or Metastatic NSCLC Following EGFR-TKI Failur](https://onco.cc/trials/nct06970782/), [VISION (tepotinib)](https://onco.cc/trials/nct02864992/)
- people: [Alexander Drilon](https://onco.cc/people/alexander-drilon/), [D. Ross Camidge](https://onco.cc/people/ross-camidge/), [Paul K. Paik](https://onco.cc/people/paul-paik/)
- key papers: [Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer](https://onco.cc/key-papers/paper-wolf-geometry-mono-1-capmatinib-nejm-2020/), [MET exon 14 splicing alterations across tumour types and their sensitivity to MET inhibitors](https://onco.cc/key-papers/paper-frampton-met-exon-14-cancer-discov-2015/), [VISION: tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations](https://onco.cc/key-papers/paper-vision-tepotinib-paik-nejm-2020/)

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JSON: https://onco.cc/api/v1/entities/met-altered-nsclc.json