Data from Tepotinib Efficacy and Safety in Patients with <i>MET</i> Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice

Abstract

<div>AbstractPurpose:<p>Primary analysis of VISION showed tepotinib had durable clinical activity in patients with <i>MET</i> exon 14 (<i>MET</i>ex14) skipping non–small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups.</p>Patients and Methods:<p>This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with <i>MET</i>ex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An <i>ad hoc</i> retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity.</p>Results:<p>152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7–53.0]. Patients aged <75 (<i>n</i> = 84) and ≥75 (<i>n</i> = 68) had ORRs of 48.8% (95% CI: 37.7–60.0) and 39.7% (95% CI: 28.0–52.3), respectively. Treatment-naïve (<i>n</i> = 69) versus previously treated (<i>n</i> = 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9–57.4) vs. 44.6% (33.7–55.9); median duration of response (95% CI): 10.8 (6.9–not estimable) vs. 11.1 (9.5–18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies.</p>Conclusions:<p>Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations.</p><p><i>See related commentary by Rosner and Spira, p. 1055</i></p></div>