Capmatinib in MET exon 14-mutated advanced NSCLC: updated results from the GEOMETRY mono-1 study.

Background Capmatinib, a selective MET inhibitor, is approved in the USA and Japan for the treatment of patients (pts) with MET exon 14 skipping mutation (METex14) advanced non-small-cell lung cancer (NSCLC) based on the multi-cohort phase II GEOMETRY mono-1 study. This is the first report on expansion Cohort 7 in first line (1L) METex14 NSCLC pts, with updates to previously reported results (Wolf et al, NEJM 2020) for METex14 pts.

At congress, it is planned to include updated data from later cut-off!

Methods In GEOMETRY mono-1, pts were assigned to cohorts based on previous lines of therapy and MET status (METex14 or MET amplification). This efficacy analysis includes patients with METex14 NSCLC who were treatment-naive (Cohort 5b and 7) and those who had previously received 1L or 2L of therapy (expansion Cohort 6 and Cohort 4) for their advanced disease (data cutoff: Sep 18, 2020). Evaluated outcomes included ORR, DOR, and PFS, all by BIRC; and OS. The safety analysis includes all patients enrolled.

Results In total, 160 pts with METex14 who received capmatinib 400 mg BID were analyzed. ORR of 65.6% (95% CI 46.8-81.4) for the treatment-naive expansion Cohort 7 was in line with that previously reported for Cohort 5b (Table). Though Cohort 7 data are still immature, median PFS was 10.8 mo (95% CI 6.87-not estimable [NE]). Mature median OS was 20.8 mo (95% CI 12.4-NE) in Cohort 5b and 13.6 mo (95% CI 8.6-22.2) in Cohort 4. Median OS for Cohorts 6 and 7 and DOR for Cohort 7 are not yet reached. The safety profile remained unchanged across all study cohorts (N=373): 98.4% of pts reported AEs (68.6% Grade [G] 3/4) regardless of causality and 16.1% reported AEs leading to discontinuation (10.5% G3/4). The most common AEs (≥20% all G) were peripheral edema (54.2%), nausea (45.0%), vomiting (28.2%), increased blood creatinine (26.5%), dyspnea (23.3%), fatigue (22.3%), and decreased appetite (21.2%).

Conclusions Results of Cohort 7 confirm those previously reported for Cohort 5b showing higher efficacy of capmatinib when used as 1L in METex14 NSCLC pts. A clinically meaningful median OS of 20.8 mo in 1L (Cohort 5b) and of 13.6 mo in relapse (Cohort 4) was also observed and, together with the continued manageable toxicity profile, the data support capmatinib as a valuable targeted treatment option for METex14 NSCLC pts.

Publication History

Article published online:
11 May 2022