2110 - Results of the GEOMETRY mono-1 phase II study for evaluation of the MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated advanced non-small cell lung cancer (NSCLC)

Background

MET mutations leading to exon 14 deletion (METΔex14) occur in 3-4% of NSCLCs. Capmatinib is a highly potent and selective MET inhibitor. GEOMETRY mono-1 is a phase II, multi-cohort, multicenter study (NCT02414139) evaluating capmatinib in pts with METΔex14 mutated or MET amplified advanced NSCLC. Here we present data from pts with METΔex14 mutation who received either 1–2 prior lines of therapy (Cohort 4) or were treatment-naive (Cohort 5b).

Methods

Eligible pts were ≥18 years of age, ECOG PS 0–1 and had ALK and EGFR wt, stage IIIB/IV NSCLC (any histology). Pts with METΔex14 mutation (centrally confirmed) were assigned to Cohorts 4 and 5b regardless of MET amplification status/gene copy number and received capmatinib tablets 400 mg twice daily. The primary endpoint was overall response rate (ORR) by BIRC per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by BIRC.

Results

As of 9-Aug-2018, 94 pts with METΔex14 mutated advanced NSCLC had ≥18 weeks of follow-up (or discontinued earlier) and were included in this analysis (Cohort 4: 69 of 69 pts in 2^nd or 3^rd line; Cohort 5b: 25 of 28 treatment-naive pts). Treatment was ongoing for 20.3% and 44.0% of pts in Cohorts 4 and 5b, respectively. ORR by BIRC assessment was 39.1% (95% CI, 27.6-51.6) in cohort 4 and 72.0% (95% CI, 50.6-87.9) in cohort 5b. All responses were confirmed. DOR data is not mature with a median duration of follow-up of 5.6 months. Preliminary activity in patients with brain metastases was also observed. The most common AEs (≥ 20% all grades) across all cohorts (1-6, n=302), regardless of causality, were peripheral edema (49.0%), nausea (43.4%), vomiting (28.5%), blood creatinine increased (24.5%), dyspnea (24.2%), decreased appetite (21.2%) and fatigue (20.9%). Majority of these AEs was grade 1/2.

Conclusions

Capmatinib has demonstrated a clinically meaningful response rate and a manageable toxicity profile in pts with METΔex14 mutated NSCLC, particularly in treatment naive pts where the ORR by BIRC is 72%. Differential benefit from 1L to pretreated pts seem to highlight the need for earlier diagnostic testing and prompt treatment of this challenging patient population.

Clinical trial identification

EudraCT: 2014-003850-15; NCT02414139. Release date 13-Feb-2018.

Editorial Acknowledgement