Capmatinib in MET Exon 14–Mutated Advanced NSCLC (GEOMETRY Mono-1 Study)

Capmatinib offers deep and durable responses with a manageable toxicity for patients with MET exon 14–mutated advanced profile non–small-cell lung cancer (NSCLC) regardless of line of therapy.

Capmatinib is a highly potent and selective MET inhibitor. Previous data from the GEOMETRY mono-1 study showed a clinically meaningful overall response rate (ORR) and manageable toxicity profile for capmatinib 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). At the American Society of Clinical Oncology 2021 annual meeting, researchers reported 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.¹

GEOMETRY mono-1 was a phase 2, multicohort, multicenter study evaluating capmatinib in patients with MET exon 14–mutated or MET-amplified advanced NSCLC across 6 cohorts. Adult patients with Eastern Cooperative Oncology Group performance status 0 or 1, wild-type ALK and EGFR, and stage IIIB or stage IV NSCLC were eligible. Patients with MET exon 14–mutated NSCLC (centrally confirmed) were assigned (regardless of MET amplification status/gene copy number) to cohorts 4 and 5b. These patients received capmatinib tablets 400 mg twice daily. The primary efficacy end point was ORR by blinded independent review committee (BIRC) per RECIST version 1.1. A key secondary end point was DOR by BIRC.¹

As of November 8, 2018, 97 patients with MET exon 14–mutated NSCLC were evaluable for efficacy: 69 patients in cohort 4; 28 patients in cohort 5b.¹ In cohort 4, the ORR by BIRC was 40.6% (95% confidence interval [CI], 28.9%-53.1%). In cohort 5b, the ORR by BIRC was 67.9% (95% CI, 47.6%-84.1%).¹ While still immature at the time of this analysis, data regarding DOR are promising: median DOR (95% CI) by BIRC was 9.7 months (5.6-13.0) and 8.4 months (12.6-not evaluable) for cohorts 4 and 5b, respectively.¹ Median PFS (95% CI) by BIRC was 5.4 months (4.2-7.0) and 12.4 months (8.2-23.4) for cohorts 4 and 5b, respectively.¹

Safety profile remains favorable and unchanged. The most common adverse events (≥25% all grades) seen with capmatinib across all cohorts (n = 373) were peripheral edema (54%), nausea (45%), vomiting (28%), and increased blood creatinine (27%).¹ The majority of these adverse events were grade 1 or 2.¹

Researchers concluded that these data confirm capmatinib’s status as a promising new treatment for patients with MET exon 14–mutated advanced NSCLC regardless of the line of therapy, offering deep and durable responses with a manageable toxicity profile.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. Presented at: 2021 American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021. Abstract 9020.