The ongoing, multicohort, phase 2 GEOMETRY mono-1 study is designed to evaluate the efficacy and safety of capmatinib in adult patients with EGFR wild-type, advanced non–small-cell lung cancer (NSCLC). Capmatinib is a kinase inhibitor that has shown promising efficacy in patients with MET exon 14 (METex14)-mutated NSCLC who were pretreated (cohort 4) or treatment-naïve (cohort 5b). Results for patients in the expansion cohort 6 with either high-level MET amplification (gene copy number [GCN] ≥10) or METex14 mutation (any MET GCN) whose disease progressed on 1 prior line of systemic therapy were reported at the 2020 ASCO Annual Meeting.
The phase 2 GEOMETRY mono-1 study enrolls adult patients with stage IIIB/IV NSCLC of any histology, Eastern Cooperative Oncology Group performance status grade 0 or 1, with ALK and EGFR wild-type. Patients receive capmatinib tablets 400 mg twice daily, with or without food. Primary outcome measures include overall response rate (ORR) and duration of response (DOR) by blinded independent review committee per Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points include investigator-assessed ORR, DOR, disease control rate, progression-free survival (PFS), and safety.
As of January 6, 2020, 34 patients with NSCLC were included in the current analysis. Of these, 31 had METex14 mutation and 3 had high-level MET amplification. Stable brain metastases were present at baseline in 7 (22.6%) patients with METex14 mutation and 1 (33.3%) patient with high-level MET amplification. At the time of data cutoff, 13 of 31 patients with METex14 and 0 of 3 patients with high-level MET amplification were still receiving treatment. The primary reason for treatment discontinuation was progression of disease.
In patients with METex14-mutated NSCLC, assessment by blinded independent review committee found the ORR was 48.4%. The median DOR, not yet mature, was 6.93 months (95% confidence interval [CI], 4.17-not estimable). The median PFS, also not yet mature, was 8.11 months (95% CI, 4.17-9.86). Investigator-assessed responses were similar to the blinded independent review committee assessments.
Of 34 NSCLC patients enrolled in this cohort, only 3 had high-level MET amplification. This was due to challenges in enrollment. All 3 patients had stable disease per blinded independent review committee assessment and were on treatment for 48, 85, and 97 days.
In this expansion cohort, the most common treatment-related adverse events (≥25%, all grades) were peripheral edema (64.7%), nausea (35.3%), fatigue (29.4%), back pain (26.5%), and vomiting (26.5%).
The investigators concluded that capmatinib was confirmed to be efficacious in second-line treatment of patients with METex14-mutated NSCLC. Capmatinib was found to have a favorable safety profile. This is the first cohort in which capmatinib was administered without fasting restriction.Source: 2020 ASCO Annual Meeting. Abstract 9520.