GEOMETRY Mono-1: Capmatinib in MET Exon 14–Mutated Advanced NSCLC

The phase 2 GEOMETRY mono-1 study showed a clinically meaningful overall response rate (ORR) and overall survival (OS) and manageable toxicity profile for capmatinib, a selective MET inhibitor, in patients with MET exon 14–mutated non–small-cell lung cancer (NSCLC) who had received 1 to 2 prior lines of treatment (cohort 4) and in treatment-naïve patients (cohort 5b). Additional efficacy results for capmatinib in MET exon 14–mutated NSCLC, including duration of response (DOR) and progression-free survival (PFS), as well as the updated ORR results, were reported at ASCO 2021.¹

Eligible patients were adults with Eastern Cooperative Oncology Group performance status 0 or 1, wild-type ALK and EGFR, and stage IIIB or stage IV NSCLC. Patients with centrally confirmed MET exon 14–mutated NSCLC were assigned regardless of MET amplification status/gene copy number to receive capmatinib tablets 400 mg twice daily. The primary efficacy end point was ORR per RECIST version 1.1 and a key secondary end point was DOR, both by blinded independent review committee (BIRC).¹

Patients with MET exon 14–mutated NSCLC were evaluable for efficacy (n = 97, cohort 4: 69 patients; cohort 5b: 28 patients, at data cutoff of November 8, 2018).¹ The ORR by BIRC was 40.6% (95% confidence interval [CI], 28.9%-53.1%) in cohort 4 and 67.9% (95% CI, 47.6%-84.1%) in cohort 5b.¹ Median DOR (95% CI) by BIRC was 9.7 months (cohort 4: range, 5.6-13.0) and 12.6 months (cohort 5b: range, 5.6-not evaluable [NE]).¹ Median PFS (95% CI) by BIRC was 5.4 months (range, 4.2-7.0 months) and 12.4 months (range, 8.2-23.4 months) while median OS (95% CI) was 13.6 months (8.6-22.2) and 20.8 months (12.4-NE), for cohorts 4 and 5b, respectively.¹

Safety profile remains favorable and unchanged with the most common adverse events (≥25% all grades; the majority grade 1 or 2) seen with capmatinib across all cohorts (n = 373: peripheral edema, 54.2%; nausea, 45.0%; and vomiting, 28.2%).¹

These data confirm the status of capmatinib as a promising new treatment offering deep and durable responses with a manageable toxicity profile for patients with MET exon 14–mutated advanced NSCLC regardless of the line of therapy.¹

Reference

1. Wolf J, Seto T, Han J-Y, et al. Capmatinib in MET exon 14-mutated, advanced NSCLC: updated results from the GEOMETRY mono-1 study. American Society of Clinical Oncology (ASCO), June 2021; Abstract 9020.