O13-4 Efficacy and intracranial activity of tepotinib in Japanese patients with MET exon 14 skipping (METex14) NSCLC (VISION)

Abstract

Tepotinib is a highly selective MET inhibitor, approved in Japan for advanced METex14 skipping NSCLC, which occurs in 3-4% of NSCLC patients (pts). Brain metastases (BMs) are reported in 20-40% of pts, presenting a high unmet need with a poor prognosis. Tepotinib crosses the blood-brain barrier and has demonstrated intracranial activity in preclinical MET-driven lung cancer. In the phase II VISION study (NCT02864992), pts in Cohorts A+C with METex14 skipping NSCLC, detected by liquid or tissue biopsy, received 500 mg QD oral tepotinib. The primary endpoint was ORR per RECIST v1.1 by independent review committee (IRC). An ad hoc retrospective analysis of brain lesions was conducted by IRC using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. By data cut-off (Feb 1, 2021), 275 pts with ≥3 months' follow-up from Cohorts A+C were evaluable for efficacy (49.1% male, median age 73 years [range: 41-94], 49.8% treatment-naÏve). ORR across treatment lines was 49.1% (95% CI: 43.0, 55.2), with mDOR of 13.8 months (95% CI: 9.9, 19.4), mPFS of 10.8 months (95% CI: 8.5, 12.4), and mOS of 19.7 months (95% CI: 15.6, 22.1). Per RECIST v1.1, 34 pts had BM at baseline; systemic ORR was 58.8% (95% CI: 40.7, 75.4). Of 38 pts from Japan, 68.4% were male, median age was 73 years [range: 62-87], and 47.3% were treatment-naÏve. ORR across treatment lines was 60.5% (95% CI: 43.4, 76.0), with mDOR of 18.5 months (95% CI: 8.3, ne), mPFS of 19.9 months (95% CI: 8.3, ne), and mOS of 20.4 months (95% CI: 16.3, ne). In Cohort A (data cut-off; Jul 1, 2020), 15 pts were evaluable by RANO-BM (12 received prior radiotherapy). Intracranial disease control was achieved in 5 of 7 pts with target lesions (all PRs), and 7 of 8 pts with non-target lesions. Tepotinib demonstrated robust systemic activity in pts with METex14 skipping NSCLC including in Japanese pts, and showed intracranial activity in pts with BM.