Capmatinib Benefits Adults with Advanced NSCLC and MET Exon 14 Skipping Mutation
- This prospective, international, open-label, multiple-cohort phase 2 trial evaluated the safety and efficacy of capmatinib in patients with advanced non–small-cell lung cancer (NSCLC) who had a MET exon 14 skipping mutation or MET amplification
- In the cohorts with a MET exon 14 skipping mutation, complete or partial response was detected among 41% of 69 previously treated patients and 68% of 28 newly diagnosed patients; median duration of response was 9.7 and 12.6 months, respectively
- 14 patients with a MET exon 14 skipping mutation had brain metastases at baseline, of whom 13 had neuroradiologic data evaluated; seven showed intracranial response, including four with complete response
- Capmatinib showed limited activity in 210 patients who had MET-amplified NSCLC, although in the cohort of patients with GCN ≥10, RR was 29% and 41% respectively in previously treated and treatment naïve patients
- In a safety analysis of 364 patients, the most frequent treatment-related adverse events were peripheral edema (51% of patients, grade 3/4 in 9%), nausea (45%/2%), vomiting (28%/2%) and increased blood creatinine level (24%/0%)
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Rebecca S. Heist, MD, MPH, hematologist/oncologist at the Mass General Cancer Center, and colleagues recently reported exciting results from the GEOMETRY mono-1 study in The New England Journal of Medicine. This phase 2 study investigated capmatinib, a new highly selective MET receptor inhibitor, in adults with advanced NSCLC who had a MET exon 14 skipping mutation or MET amplification.
307 patients used oral capmatinib 400 mg twice daily under fasting conditions. 57 patients were treated without fasting restrictions and were considered only in the safety analysis.
MET Exon 14 Skipping Mutation
- Complete or partial response—41% of 69 previously treated patients and 68% of 28 newly diagnosed patients
- Median duration of response—9.7 months and 12.6 months
- Median progression-free survival—5.4 months and 12.4 months
Antitumor activity and duration of response seemed to be independent of whether patients had concurrent MET amplification.
13 of 14 patients with brain metastases at baseline had neuroradiologic data evaluated. Seven showed intracranial response, including four with complete response. Three of the seven had brain radiotherapy previously.
MET Amplification Only
Three cohorts, representing 126 patients who had tumor tissue with a gene copy number (GCN) <10, were closed for futility at the interim analysis.
Capmatinib showed activity in 84 patients with GCN ≥10, but the overall response rates were lower than prespecified thresholds.
The most frequent treatment-related adverse events were peripheral edema (51% of patients, grade 3/4 in 9%), nausea (45%/2%), vomiting (28%/2%) and increased blood creatinine level (24%/0%).
Capmatinib is now FDA-approved for adults with metastatic NSCLC whose tumors have a mutation that leads to MET exon 14 skipping as detected by an FDA-approved test. This indication—the first for the drug—was approved under accelerated review, and continued approval may be contingent on the results of confirmatory trials.
Broad molecular profiling is warranted before decision-making about first-line therapy. In an analysis of 73 patients in this study who had a MET exon 14 skipping mutation, the results of next-generation sequencing were 99% concordant with those of reverse transcriptase polymerase chain reaction.
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