On August 10, 2022, the U.S. Food and Drug Administration (FDA) granted regular approval to capmatinib (Tabrecta) for adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping, as detected by an FDA-approved test.
Capmatinib was previously granted accelerated approval for the same indication on May 6, 2020, based on initial overall response rate and duration of response in the GEOMETRY mono-1 trial (ClinicalTrials.gov identifier: NCT02414139), a multicenter, nonrandomized, open-label, multicohort study. The conversion to regular approval was based on data from an additional 63 patients, as well as an additional 22 months of follow-up to assess durability of response and verify clinical benefit.
Efficacy was demonstrated in 160 patients with metastatic NSCLC with MET exon 14 skipping mutations. Patients received capmatinib at 400 mg orally twice daily until disease progression or unacceptable toxicity.
The primary efficacy measures were overall response rate and duration of response as determined by a blinded independent review committee. Among 60 treatment-naive patients, overall response rate was 68% (95% confidence interval [CI] = 55%–80%), with a duration of response of 16.6 months (95% CI = 8.4–22.1). Among 100 previously treated patients, overall response rate was 44% (95% CI = 34%–54%), with a duration of response of 9.7 months (95% CI = 5.6–13).
The median age of patients was 71 years (range = 48–90 years). Selected demographics were reported as follows:
Among previously treated patients, 81% received one, 16% received two, and 3% received three prior lines of systemic therapy. Among previously treated patients, 86% received prior platinum-based chemotherapy.
The most common adverse reactions (≥ 20%) in patients treated with capmatinib were edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased appetite.
The recommended capmatinib dose is 400 mg orally twice daily with or without food.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration. The application reviews may be ongoing at the other regulatory agencies.
This review also used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review, Breakthrough designation, and Orphan Drug designation.