MET exon 14 and MET-amplified non-small-cell lung cancer
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.
Overview
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.
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.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowSkin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
- Check before combiningFood and drink: Amivantamab
No food effect (intravenous or subcutaneous antibody).
- Check before combiningFood and drink: Capmatinib & tepotinib
Capmatinib: photosensitivity, use sun protection. Tepotinib: take with food.
- Check before combiningHeart rhythm (QT): Osimertinib
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
See all on the product pages:AmivantamabCapmatinibCapmatinib & tepotinibCarboplatinDocetaxelOsimertinibPemetrexedSavolitinibTelisotuzumab vedotinTepotinib·Printable cards in the navigator
Anatomy and lymph node drainage
- Central airways (squamous, small-cell)
- Periphery (adenocarcinoma)
- Apex (Pancoast)
- Pleura (mesothelioma)
- Thymus (anterior mediastinum)
- Nodes: hilar (N1)
- Nodes: mediastinal (N2)
- Nodes: supraclavicular (N3)
Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.
- Central airways (squamous, small-cell)
- Periphery (adenocarcinoma)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)
- Apex (Pancoast)
- Pleura (mesothelioma)MET exon 14 skipping adenocarcinoma or sarcomatoid carcinoma (capmatinib, tepotinib)
- Thymus (anterior mediastinum)MET exon 14 skipping adenocarcinoma or sarcomatoid carcinoma (capmatinib, tepotinib) · MET amplification as acquired resistance in EGFR-mutated adenocarcinoma (osimertinib plus savolitinib, amivantamab)
- hilar (N1)
- mediastinal (N2)
- supraclavicular (N3)
Same organ: Non-small-cell lung cancer, Lung cancer (all types), Small-cell lung cancer, Mesothelioma, Pleural mesothelioma, Thymoma and thymic carcinoma, Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours), Inflammatory myofibroblastic tumour (IMT), EGFR-mutated non-small-cell lung cancer, ALK-positive non-small-cell lung cancer, KRAS G12C-mutant non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, BRAF V600E-mutant non-small-cell lung cancer, HER2-mutant non-small-cell lung cancer, NTRK fusion-positive non-small-cell lung cancer, PD-L1-high non-small-cell lung cancer without a driver mutation, Resectable stage I to III non-small-cell lung cancer, Unresectable stage III non-small-cell lung cancer, Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid)
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.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Capmatinib (GEOMETRY mono-1) or tepotinib (VISION); platinum-pemetrexed with or without pembrolizumab if the inhibitor is not tolerated or after it.
Osimertinib plus savolitinib (SAVANNAH, SACHI) where available; amivantamab plus chemotherapy; platinum-pemetrexed.
Telisotuzumab vedotin (LUMINOSITY) after platinum chemotherapy; TeliMET NSCLC-01 versus docetaxel is confirmatory.
Subtypes & biomarkers
top- 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)
- 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
How often this target appears
- 2015MET exon 14 skipping shown to be a targetable driver with crizotinib responses
- 2020GEOMETRY mono-1: capmatinib approved; VISION: tepotinib reported
- 2021Tepotinib approved; savolitinib approved in China
- 2024LUMINOSITY: telisotuzumab vedotin response rate 35 percent in c-Met high tumours
- 2025Telisotuzumab vedotin approved; SACHI: osimertinib plus savolitinib for MET-amplified resistance
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 9 changes by month →- 2026-09-17This recordMET exon 14 and MET-amplified non-small-cell lung cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2025MilestoneTelisotuzumab vedotinTelisotuzumab vedotin approved; SACHI: osimertinib plus savolitinib for MET-amplified resistance
A milestone in how this cancer is treated.
- 2024Trial resultLUMINOSITYLUMINOSITY reported
ORR 28.
- 2024MilestoneLUMINOSITYLUMINOSITY: telisotuzumab vedotin response rate 35 percent in c-Met high tumours
A milestone in how this cancer is treated.
- 2022-01RegulatoryTelisotuzumab vedotinTelisotuzumab vedotin: designation granted (US)
Breakthrough Therapy designation, c-MET overexpressing NSCLC
- 2021MilestoneTepotinibTepotinib approved; savolitinib approved in China
A milestone in how this cancer is treated.
What is in development for MET exon 14 and MET-amplified non-small-cell lung cancer, drawn from the whole corpus: 6 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 1
Trials under way · 3
- TeliMET NSCLC-01 · phase 3 · AbbVie
- Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib · phase 2 · AstraZeneca
- Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) · phase 2 · EMD Serono Research & Development Institute, Inc.
Trials reported · 2
- GEOMETRY mono-1 · phase 2 · 2020 · positive
- LUMINOSITY · phase 2 · 2024 · positive
Open problems and what is being done
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.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
| Taiwan | none recorded | 0 | 746 | 8,966 | - | ||
Guangzhou · hospital Programme: Guangdong Lung Cancer Institute | China | none recorded | 0 | 704 | 7,832 | - | |
Philadelphia, PA · hospital | United States | none recorded | 0 | 695 | 9,931 | - | |
| China | none recorded | 0 | 539 | 6,491 | - | ||
Aurora, CO · cancer center Programme: Oncogene-driven lung cancer, Lung cancer SPORE | United States | 0 | 483 | 13,480 | - | ||
Candiolo · cancer center | Italy | none recorded | 0 | 324 | 4,466 | - | |
Nashville, TN · cancer center | United States | 0 | 269 | 9,027 | - | ||
Ljubljana · cancer center | Slovenia | none recorded | 0 | 187 | 2,566 | - | |
Washington, DC · cancer center | United States | 0 | 100 | 2,434 | - | ||
Neu-Isenburg · consortium | Germany | none recorded | 0 | 94 | 1,947 | none recorded | - |
Chicago, IL · consortium | United States | none recorded | 0 | 42 | 482 | - | |
Tokyo · government | Japan | none recorded | 0 | not matched | - | - | |
Osaka · consortium | Japan | none recorded | 0 | not matched | - | - | |
Atlanta, GA · cancer center Programme: EGFR-mutant lung cancer (FLAURA) | United States | 0 | not matched | - | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with MET exon 14 and MET-amplified non-small-cell lung cancer but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about MET exon 14 and MET-amplified non-small-cell lung cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example MET exon 14 skipping by RNA or DNA sequencing, MET gene copy number by fluorescence in situ hybridisation or sequencing, c-Met immunohistochemistry, MET amplification in plasma or tissue at progression on osimertinib, Peripheral oedema and creatinine on MET inhibitors), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include MET exon 14 skipping adenocarcinoma or sarcomatoid carcinoma, De novo high-level MET amplification, MET amplification as acquired resistance in EGFR-mutated adenocarcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Advanced MET exon 14, first line or later
- For my situation (advanced met exon 14, first line or later), which of the standard options do you recommend and why?Why: Guideline options include: Capmatinib (GEOMETRY mono-1) or tepotinib (VISION); platinum-pemetrexed with or without pembrolizumab if the inhibitor is not tolerated or after it.
- Am I a candidate for Capmatinib, Tepotinib, Capmatinib & tepotinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of GEOMETRY mono-1 and Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
MET amplification after osimertinib in EGFR-mutated disease
- For my situation (met amplification after osimertinib in egfr-mutated disease), which of the standard options do you recommend and why?Why: Guideline options include: Osimertinib plus savolitinib (SAVANNAH, SACHI) where available; amivantamab plus chemotherapy; platinum-pemetrexed.
- Am I a candidate for Osimertinib, Savolitinib, Amivantamab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib and 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 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
c-Met overexpression, previously treated non-squamous
- For my situation (c-met overexpression, previously treated non-squamous), which of the standard options do you recommend and why?Why: Guideline options include: Telisotuzumab vedotin (LUMINOSITY) after platinum chemotherapy; TeliMET NSCLC-01 versus docetaxel is confirmatory.
- Am I a candidate for Telisotuzumab vedotin, Docetaxel, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of LUMINOSITY and TeliMET NSCLC-01 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of TeliMET NSCLC-01, Telisotuzumab adizutecan, Savolitinib, Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “MET amplification has no agreed threshold and results differ between assays”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Peripheral oedema limits the dose of every MET inhibitor and has no good treatment”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with MET exon 14 and MET-amplified non-small-cell lung cancer, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
6targets
4drugs
12companies
10pathways
2terms
4trials
6people
2Latest papers
topQuery for this cancer: (TITLE:"MET exon 14 and MET-amplified non-small-cell lung cancer" OR ABSTRACT:"MET exon 14 and MET-amplified non-small-cell lung cancer" OR TITLE:"MET exon 14 skipping lung cancer" OR ABSTRACT:"MET exon 14 skipping lung cancer" OR TITLE:"METex14 NSCLC" OR ABSTRACT:"METex14 NSCLC" OR TITLE:"MET-amplified lung cancer" OR ABSTRACT:"MET-amplified lung cancer" OR TITLE:"c-Met overexpressing NSCLC" OR ABSTRACT:"c-Met overexpressing NSCLC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about MET exon 14 and MET-amplified non-small-cell lung cancer, not a curated reading list.
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