Oral MET inhibitor capmatinib showed clinical activity in patients with MET exon 14–mutated advanced non–small cell lung cancer (NSCLC), including those with brain metastases. The results of the phase 2 GEOMETRY mono-1 trial were recently published in the New England Journal of Medicine.
The trial (ClinicalTrials.gov Identifier: NCT02414139) included 364 patients with MET-dysregulated advanced NSCLC who were grouped into cohorts on the basis of prior lines of therapy and MET status (MET exon 14 skipping mutation or number of MET amplification gene copy numbers).
Among patients with MET exon 14–mutated disease, the overall response rate was 41% (95% CI, 29%-53%) for those previously treated, which exceeded the 35% prespecified threshold for clinically relevant activity. The response rate was 68% (95% CI, 48%-84%) for those who had no prior treatment, which exceeded the 55% prespecified threshold for clinically relevant activity.
Activity was also seen in patients with brain metastases, with 7 of 13 patients with a MET exon 14 skipping mutation achieving an intracranial response — 4 of which were complete responses.
Among patients with MET-amplified disease, the response rates were highest for previously treated and untreated patients with a gene copy number of at least 10 (29% and 40%, respectively), but neither were high enough to exceed the prespecified thresholds for clinically relevant activity.
The most common treatment-related adverse events were peripheral edema, nausea, vomiting, and increased blood creatinine level. One patient died from pneumonitis, which was “suspected to be related to capmatinib.”
The study authors concluded that capmatinib “may be” a “new therapeutic option” in patients with MET exon 14–mutated advanced NSCLC.
Wolf J, Seto T, Han J, et al. Capmatinib in MET exon 14–mutated or MET-amplified non–small-cell lung cancer. N Engl J Med. 2020;383:944-957. doi:10.1056/NEJMoa2002787