{"entity":{"id":"nct02864992","kind":"trial","name":"VISION (tepotinib)","aka":["VISION","MS200095-0022","Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)"],"tldr":"VISION showed that a once-daily MET tablet shrank about half of advanced lung cancers driven by a MET exon 14 skipping mutation, whether the mutation was found in blood or in tumour tissue, which led to tepotinib's approvals in Japan, the United States and Europe.","summary":"VISION (NCT02864992; sponsor code MS200095-0022) is an open-label, single-arm phase 2 study of tepotinib 500 mg once daily in advanced non-small-cell lung cancer with MET exon 14 skipping, detected in circulating tumour DNA, tumour tissue or both, with a later cohort in MET amplification. The primary endpoint was objective response by independent review among patients followed for at least nine months.\n\nIn the NEJM 2020 primary analysis (Paik and colleagues), 152 patients had received tepotinib by 1 January 2020 and 99 had at least nine months of follow-up. The independent-review response rate in the combined-biopsy group was 46 percent (95 percent CI 36 to 57), with a median duration of response of 11.1 months (95 percent CI 7.2 to not estimable). Response rates were 48 percent among 66 patients in the liquid-biopsy group and 50 percent among 60 in the tissue-biopsy group; 27 patients were positive by both. The investigator-assessed response rate was 56 percent and did not depend on previous treatment for advanced disease. Grade 3 or higher treatment-related adverse events occurred in 28 percent, including peripheral oedema in 7 percent, and adverse events led to permanent discontinuation in 11 percent. A molecular response in circulating free DNA was seen in 67 percent of patients with matched samples.\n\nJapan approved tepotinib in 2020, the United States in 2021 (with full approval in 2024) and the EU in 2022. The registry lists 337 participants across all cohorts and the study as active, not recruiting, with completion expected in August 2026. Capmatinib (GEOMETRY mono-1) is the other approved MET exon 14 inhibitor; the Pluvicto prostate-cancer trial also named VISION is a different study (id vision, NCT03511664).","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT02864992","url":"https://clinicaltrials.gov/study/NCT02864992"},{"label":"NEJM 2020","url":"https://doi.org/10.1056/NEJMoa2004407"}],"tags":["pipeline","issue-92"],"related":[],"cancers":["nsclc","met-altered-nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["met"],"drugs":["tepotinib"],"companies":["merck-kgaa"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vision-tepotinib-paik-nejm-2020","paper-nct02864992-jama-oncol-2023-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02864992","phase":"2","setting":"Advanced or metastatic non-small-cell lung cancer with a confirmed MET exon 14 skipping mutation: tepotinib 500 mg once daily until progression, in cohorts defined by liquid biopsy, tissue biopsy or both","sponsor":"EMD Serono Research & Development Institute, Inc.","result":"Independent-review objective response 46% (95% CI 36 to 57) among 99 patients with at least nine months of follow-up; median duration of response 11.1 months (Paik, NEJM 2020).","started":"2016-09-13","startedType":"actual","yearReported":2020,"enrolled":337,"enrolledBasis":"registry","outcomes":[{"endpoint":"Objective response rate by independent review, combined-biopsy group (at least 9 months of follow-up)","primary":true,"unit":"%","arms":[{"name":"Tepotinib 500 mg daily","n":99,"value":46,"note":"95% CI 36 to 57; 152 patients had received tepotinib by the 1 January 2020 cutoff"}],"source":"https://doi.org/10.1056/NEJMoa2004407"},{"endpoint":"Median duration of response by independent review, combined-biopsy group","unit":"months","arms":[{"name":"Tepotinib 500 mg daily","n":99,"value":11.1,"note":"95% CI 7.2 to not estimable"}],"source":"https://doi.org/10.1056/NEJMoa2004407"},{"endpoint":"Objective response rate by independent review, liquid-biopsy group","unit":"%","arms":[{"name":"Tepotinib 500 mg daily","n":66,"value":48,"note":"95% CI 36 to 61"}],"source":"https://doi.org/10.1056/NEJMoa2004407"},{"endpoint":"Objective response rate by independent review, tissue-biopsy group","unit":"%","arms":[{"name":"Tepotinib 500 mg daily","n":60,"value":50,"note":"95% CI 37 to 63"}],"source":"https://doi.org/10.1056/NEJMoa2004407"},{"endpoint":"Grade 3 or higher treatment-related adverse events","unit":"%","arms":[{"name":"Tepotinib 500 mg daily","n":152,"value":28,"note":"Peripheral oedema 7%; adverse events led to permanent discontinuation in 11%"}],"source":"https://doi.org/10.1056/NEJMoa2004407"}],"replication":"GEOMETRY mono-1 (capmatinib) reported response rates of 68 percent in treatment-naive and 41 percent in previously treated MET exon 14 skipping lung cancer; both drugs are approved for this population, so the class effect is established."},"route":"/trials/nct02864992/","neighbours":{"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"met-altered-nsclc","kind":"cancer","name":"MET exon 14 and MET-amplified non-small-cell lung cancer","route":"/cancers/met-altered-nsclc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"drug":[{"id":"capmatinib-tepotinib","kind":"drug","name":"Capmatinib & tepotinib","route":"/drugs/capmatinib-tepotinib/"},{"id":"tepotinib","kind":"drug","name":"Tepotinib","route":"/drugs/tepotinib/"}],"company":[{"id":"merck-kgaa","kind":"company","name":"Merck KGaA (EMD Serono)","route":"/companies/merck-kgaa/"}],"paper":[{"id":"paper-nct02864992-jama-oncol-2023-update","kind":"paper","name":"Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial","route":"/key-papers/paper-nct02864992-jama-oncol-2023-update/"},{"id":"paper-vision-tepotinib-paik-nejm-2020","kind":"paper","name":"VISION: tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations","route":"/key-papers/paper-vision-tepotinib-paik-nejm-2020/"}]}}