SYST-06 INTRACRANIAL ACTIVITY OF TEPOTINIB IN PATIENTS WITH MET EXON 14 (METEX14) SKIPPING NSCLC ENROLLED IN VISION. (5th August 2022)

• Record Type: Journal Article
• Authors: Leighl, Natasha; Bestvina, Christine; Patel, Jyoti; Le, Xiuning; Veillon, Remi; Anderson, Ian; Demedts, Ingel; Garassino, Marina Chiara; Mazières, Julien; Morise, Masahiro; Smit, Egbert; Eggleton, S Peter; O'Brate, Aurora; Otto, Gordon; Bruns, Rolf; Schumacher, Karl Maria; Paik, Paul
• Is Part Of: Neuro-oncology advances. Volume 4(2022)Supplement 1
• Page Start: i22
• Page End: i22
• Publication Date: 2022-08-05
• Subjects: 616.99481
• DOI: 10.1093/noajnl/vdac078.085
• Languages: English
• ISSNs: 2632-2498

Abstract

Abstract: BACKGROUND: Brain metastases (BMs) occur in 20–40% of patients with METex14 skipping NSCLC. Tepotinib, a highly selective MET inhibitor, demonstrated an objective response rate (ORR) of 49.1% and median duration of response (mDOR) of 13.8 months, in METex14 skipping NSCLC patients in the Phase II VISION study (Cohorts A+C; N=275). Here, we report the intracranial activity of tepotinib in VISION. METHODS: Patients with METex14 skipping NSCLC received oral tepotinib 500 mg QD (450 mg active moiety). Patients with BM (asymptomatic and symptomatic/stable) were eligible. Primary endpoint was systemic ORR (RECIST v1.1); a subgroup analysis in patients with BM was predefined (data cut-off: February 1, 2021). An ad-hoc retrospective analysis of brain lesions was conducted by an IRC using RANO-BM criteria. Responses were determined in patients with ≥1 evaluable post-baseline tumor assessment. For those with only non-target lesions (NTLs) per RANO-BM (enhancing and non-enhancing NTLs), disease control was defined as non-complete response (CR)/nonprogressive disease (PD). Data cut-off: July 1, 2020. RESULTS: Fifty-one patients had baseline BM (Cohorts A+C). Systemic efficacy was consistent with the overall population (ORR 52.9% [95% CI: 38.5, 67.1], mDOR 9.0 months [95% CI: 5.6, not estimable]). Fifteen patients were evaluable by RANO-BM (Cohort A); 12 received prior radiotherapy for BM (median 6.4 weeks before treatment). Systemic best objective responses (BORs) were partial response (PR, n=9), stable disease (SD, n=3), and PD (n=3). Seven patients had target CNS lesions per RANO-BM (all with prior radiotherapy); intracranial BORs were PR (n=5), SD (n=1), and PD (n=1). For patients with NTL only (n=8), one had PD, and seven achieved intracranial disease control with three patients achieving CR of the enhancing NTL. 13/15 patients achieved intracranial disease control. CONCLUSIONS: Tepotinib demonstrated robust systemic activity in patients with METex14 skipping NSCLC with BM, complemented by intracranial activity in an ad-hoc analysis using RANO-BM.