On August 10, 2022, the FDA accelerated the regular full approval of capmatinib (Tabrecta; Novartis), a tyrosine kinase inhibitor, for the treatment of metastatic non–small-cell lung cancer (NSCLC) in adults whose tumors have MET exon 13 skipping mutation, as detected by an FDA-approved test.
This approval was granted orphan drug and breakthrough therapy designations. On May 6, 2020, the FDA had granted accelerated approval to capmatinib for this indication.
This approval was based on the efficacy results of an initial 160 patients with metastatic NSCLC and MET exon 14 skipping mutation in the multicenter, nonrandomized, open-label, multicohort GEOMETRY mono-1 clinical trial, which included an additional 63 patients and an extra 22 months of follow-up to assess the durability of the responses and to verify the clinical importance of capmatinib.
The major efficacy end point was overall response rate (ORR) and duration of response (DOR) as determined by a blinded Independent Review Committee. In 60 treatment-naïve patients in the study, the ORR was 68% (95% confidence interval [CI], 55-80) and the DOR was 16.6 months (95% CI, 8.4-22.1). In 100 patients who received previous treatment, the ORR was 44% (95% CI, 34-54) and the DOR was 9.7 months (95% CI, 5.6-13).
The most common (≥20%) adverse reactions were edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased appetite.
The recommended dose of capmatinib is 400 mg orally twice daily with or without food.
