US Food and Drug Administration–approved capmatinib is an effective second-line treatment for patients with MET exon 14–mutated NSCLC.
MET exon 14–mutated disease is identified in 3% of patients with nonsquamous non–small-cell lung cancer (NSCLC) and represents a clinically unique molecular subtype.1 In the multicenter, nonrandomized, open-label, multicohort GEOMETRY mono-1 trial, researchers evaluated the oral MET inhibitor capmatinib in patients with MET exon 14–mutated NSCLC.2
GEOMETRY mono-1 enrolled 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping.2 Patients were treated with twice-daily oral capmatinib 400 mg until disease progression or unacceptable toxicity was reached.2 Key efficacy end points were overall response rate (ORR) and duration of response as determined by blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumours version 1.1.2 Other secondary end points included investigator-assessed ORR, duration of response, disease control rate, progression-free survival (PFS; BIRC and investigator assessment), and safety.3
ORR was 68% (median response duration, 12.6 months) among 28 treatment-naïve patients with MET exon 14–mutated NSCLC who received capmatinib during the study.2 ORR was 41% (median response duration, 9.7 months) among 69 previously treated patients.2
At the 2020 American Society of Clinical Oncology virtual meeting, researchers reported results for patients who enrolled in the GEOMETRY mono-1 expansion cohort known as Cohort 6.3 These patients had either MET exon 14 mutation, defined as any MET gene copy number (GCN) and disease progression after 1 prior line of systemic therapy, or high-level MET amplification, defined as GCN ≥10.3 There were 34 patients with MET exon 14–mutated NSCLC (N = 31) or high-level MET amplification (N = 3) included in this analysis as of January 6, 2020.3
BIRC assessment resulted in an ORR of 48% (median response duration, 6.9 months) among the 31 patients with MET exon 14–mutated NSCLC (not yet mature; 95% confidence interval [CI], 4.2-not evaluable).3 The median PFS was 8.1 months (not yet mature; 95% CI, 4.2-9.9).3 Among the 3 patients with high-level MET amplification, all had stable disease per blinded assessment and were on treatment for 48, 85, and 97 days.3
Among the 34 patients in Cohort 6, the most common adverse events associated with capmatinib (≥25%, all grades) were peripheral edema (65%), nausea (35%), fatigue (29%), back pain (27%), and vomiting (27%).3
Based on the results of GEOMETRY mono-1, researchers concluded that capmatinib is efficacious in the second-line for MET exon 14–mutated NSCLC patients,3 the indication for which the drug was approved by the US Food and Drug Administration in May 2020.2
References
1. Awad M, et al. J Clin Oncol. 2016;34:721-730.
2. Food and Drug Administration. FDA grants accelerated approval to capmatinib for metastatic non-small cell lung cancer. May 6, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-capmatinib-metastatic-non-small-cell-lung-cancer. Accessed January 11, 2021.
3. Groen H, et al. J Clin Oncol. 2020;38(suppl 15). Abstract 9520.
