Tepotinib Treatment in Patients With <i>MET</i> Exon 14–Skipping Non–Small Cell Lung Cancer

<jats:sec><jats:title>Importance</jats:title><jats:p>MET inhibitors have recently demonstrated clinical activity in patients with <jats:italic>MET</jats:italic> exon 14 (<jats:italic>MET</jats:italic>ex14)-skipping non–small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with <jats:italic>MET</jats:italic>ex14-skipping NSCLC in the VISION study.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with <jats:italic>MET</jats:italic>ex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (&amp;gt;18 months’ follow-up) was an independent cohort, designed to confirm findings from cohort A (&amp;gt;35 months’ follow-up). Data cutoff was November 20, 2022.</jats:p></jats:sec><jats:sec><jats:title>Intervention</jats:title><jats:p>Patients received tepotinib, 500 mg (450 mg active moiety), once daily.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary end point was objective response by independent review committee (RECIST v1.1). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Cohorts A and C included 313 patients (50.8% female, 33.9% Asian; median [range] age, 72 [41-94] years). The objective response rate (ORR) was 51.4% (95% CI, 45.8%-57.1%) with a median (m)DOR of 18.0 (95% CI, 12.4-46.4) months. In cohort C (n = 161), an ORR of 55.9% (95% CI, 47.9%-63.7%) with an mDOR of 20.8 (95% CI, 12.6-not estimable [NE]) months was reported across treatment lines, comparable to cohort A (n = 152). In treatment-naive patients (cohorts A and C; n = 164), ORR was 57.3% (95% CI, 49.4%-65.0%) and mDOR was 46.4 (95% CI, 13.8-NE) months. In previously treated patients (n = 149), ORR was 45.0% (95% CI, 36.8%-53.3%) and mDOR was 12.6 (95% CI, 9.5-18.5) months. Peripheral edema, the most common treatment-related adverse event, occurred in 210 patients (67.1%) (35 [11.2%] experienced grade ≥3 events).</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>The findings from cohort C in this nonrandomized clinical trial supported the results from original cohort A. Overall, the long-term outcomes of VISION demonstrated robust and durable clinical activity following treatment with tepotinib, particularly in the treatment-naive setting, in the largest known clinical trial of patients with <jats:italic>MET</jats:italic>ex14-skipping NSCLC, supporting the global approvals of tepotinib and enabling clinicians to implement this therapeutic approach for such patients.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02864992">NCT02864992</jats:ext-link></jats:p></jats:sec>