Primary efficacy and biomarker analyses from the VISION study of tepotinib in patients (pts) with non-small cell lung cancer (NSCLC) with METex14 skipping.

Abstract

9556 Background: Preliminary tepotinib data showed durable activity in pts with NSCLC with METex14 skipping prospectively identified by liquid (L+) or tissue (T+) biopsy. Having met target enrollment of ≥60 L+ pts & ≥60 T+ pts, we report primary data. Methods: VISION Cohort A enrolled pts with advanced EGFR/ALK wt, METex14 skipping NSCLC (asymptomatic brain metastases [BM] allowed), who received oral tepotinib 500 mg QD. On-study treatment decisions were based on investigator assessment (INV) of response. Primary endpoint was objective response rate (ORR) by independent review committee (IRC) analyzed in 3 primary ITT sets: L+ and/or T+, L+, T+. 2ary endpoints included ORR by INV, duration of response (DOR), disease control rate (DCR), PFS, OS, & safety. Preplanned analyses were performed in pts with BM at baseline (BL). BL/on-treatment ctDNA plasma samples (L+) were analyzed using a 73-gene NGS panel (Guardant360). Deep molecular responses (MR), defined as > 75% depletion of METex14, were compared with objective responses (OR). Results: By data cut-off (1 Oct 19) 151 pts received tepotinib (safety set); 99 L+/T+, 66 L+, 60 T+ pts comprised the 3 ITT sets with ≥6-month [m] follow-up. Across treatment lines (n = 44 1L, n = 55 ≥2L), primary ORR & mPFS [95% CI] in 99 L+/T+ pts were 43% [34–54] & 8.6 m [6.9–11.0] by IRC and 56% [45–66] & 9.5 m [6.7–13.5] by INV. ORR was similar in L+ or T+ pts (table) or in T+L− pts (n = 25): 40% [21–61] by IRC and 48% [28–69] by INV. Only 2 pts were T−L+. Outcomes were also comparable in pts with BM (n = 11): IRC ORR 55% [23–83] & mPFS 10.9 m [8.0–ne]. 34/51 pts (67%) with matched BL/on-treatment L+ samples had deep MR strongly associated with clinical response: 32/34 pts (94%) with MR had disease control (INV), including 29/34 pts (85%) with OR; 2/34 pts had progressive disease. Further biomarker data will be presented. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 37/151 pts (25%). 13 pts (9%) discontinued due to TRAEs. Conclusions: Tepotinib is a promising targeted therapy with durable clinical activity and manageable toxicity in pts with METex14 skipping NSCLC L+ or T+, including pts with BM. High ORR & DCR in pts with ctDNA molecular responses support that MET inhibition in METex14+ tumor cells can lead to clinical benefit. Clinical trial information: NCT02864992 . [Table: see text]