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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
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.
| Setting | Approach | Guideline |
|---|---|---|
| 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. | not mapped |
| MET amplification after osimertinib in EGFR-mutated disease | Osimertinib plus savolitinib (SAVANNAH, SACHI) where available; amivantamab plus chemotherapy; platinum-pemetrexed. | not mapped |
| c-Met overexpression, previously treated non-squamous | Telisotuzumab vedotin (LUMINOSITY) after platinum chemotherapy; TeliMET NSCLC-01 versus docetaxel is confirmatory. | not mapped |