Profiling patients with <i>MET</i> exon 14 ( <i>MET</i> ex14) skipping NSCLC with a sustained clinical benefit to tepotinib in VISION.

Abstract

8612 Background: Tepotinib is a highly selective MET inhibitor with clinical activity in patients with MET ex14 skipping NSCLC. We previously reported long-term efficacy and safety outcomes of tepotinib from VISION in patients with ≥3-years follow-up (data cut-off: May 20, 2024; Mazieres et al. ELCC 2025 [Poster 81P]). Here, we provide a subset analysis of patients from VISION who achieved long-term responses to tepotinib to identify clinical characteristics associated with durable benefit. Methods: Patients with advanced MET ex14 skipping NSCLC detected by liquid (L+) and/or tissue (T+) biopsy received tepotinib 500 mg (450 mg active moiety) once daily. The primary endpoint was objective response by independent review using RECIST v1.1. Secondary endpoints included duration of response and safety. Exploratory analyses of baseline and on-treatment liquid biopsy biomarkers were carried out for potential prognostic, predictive, or pharmacodynamic relevance. For this subset analysis, patients with a long-term response were defined as those with a duration of response (DOR) to tepotinib of &gt;36 months. Results: Of 313 patients enrolled, 26 patients had a DOR &gt;36 months (range: 36.6–78.9). In these patients, median age was 67.7 years (range: 52–84), 53.8% were male, 50.0% were White and 34.6% were Asian, 92.3% had adenocarcinoma, 53.8% had a history of smoking, and 53.8% were L+ and 65.4% were T+. Median duration of treatment was 50.7 months (range: 15.9–83.1). Seventeen patients received tepotinib as first-line and nine as second-or-later line therapy. Twenty-four patients achieved &gt;50% decrease, while six patients achieved &gt;80% decrease in the sum of longest diameters from baseline. Eighteen patients’ cancer had not progressed at the data cut-off of May 20, 2024, and 14 patients were still receiving treatment. In 12 patients who discontinued treatment, reasons for discontinuation were: adverse events (5 patients [peripheral edema in 2 patients]), disease progression per investigator (3 patients), non-compliance (1 patient), consent withdrawal (1 patient), and other reasons (2 patients). Among patients with long-term responses who stopped treatment early due to adverse events (prior to disease progression), continued responses were observed for up to 52 months after tepotinib discontinuation without any further subsequent anticancer treatment. Of nine patients who received treatment prior to tepotinib, four patients received immunotherapy alone, and eight patients received chemotherapy without immunotherapy. Baseline and on-treatment biomarker data will be presented. Conclusions: Patients who achieved long-term responses to tepotinib in VISION had similar clinical characteristics and safety outcomes to the overall population of patients from VISION (Mazieres et al. ELCC 2025 [Poster 81P]); ongoing biomarker analyses may help to further characterize these patients. Clinical trial information: NCT02864992 .