Background: Tepotinib, a highly selective MET inhibitor, has demonstrated robust and durable efficacy and safety in patients with METex14 skipping NSCLC in Cohorts A+C (data cut-off: Nov 20, 2022; follow-up: Cohort A >35 months, Cohort C >18 months) and in patients with high-level MET amplification (METamp) NSCLC in Cohort B of the Phase II VISION study (NCT02864992). We report long-term efficacy and safety outcomes from VISION in patients with ≥3-year follow-up (data cut-off: May 20, 2024).
Methods: Patients with advanced NSCLC and METex14 skipping or METamp received tepotinib 500 mg (450 mg active moiety) QD. Primary endpoint was objective response (Independent review using RECIST v1.1). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
Results: Of 313 patients enrolled in Cohorts A+C (male: 49.2%; median age: 72 years; ECOG PS 1: 73.8%; smoking history: 47.6%), the median duration of treatment was 7.5 months, and treatment was ongoing in 18 patients (first-line [1L]: 12/164; second-or-later line [2L+]: 6/149). Overall, objective response rate (ORR) was 51.8% (95% CI: 46.1, 57.4), mDOR was 18.0 months (12.6, 31.8), mPFS was 11.2 months, and mOS was 19.7 months.
In 1L patients, ORR was 57.9%, mDOR was 31.7 months, mPFS was 12.6 months, and mOS was 21.1 months, while in 2L+ patients, ORR was 45.0%, mDOR was 12.6 months, mPFS was 11.0 months, and mOS was 19.3 months. No new safety concerns were observed. Grade ≥3 TRAEs occurred in 36.1% patients, while 15.7% patients discontinued treatment due to TRAEs.
Long-term outcomes from Cohort B will also be presented.
Conclusions: Tepotinib continued to demonstrate robust and durable activity across treatment lines. Importantly, outcomes in patients with METex14 skipping were consistent with previous results, reinforcing tepotinib as a meaningful treatment option in this setting.