FDA has granted accelerated approval to Tabrecta (capmatinib) for adult patients with metastatic non-small cell lung cancer whose tumors have a mutation that leads to mesenchymal-epithelial transition exon 14 skipping as detected by an FDA-approved test.
Tabrecta is the first FDA-approved therapy to treat NSCLC with specific mutations (those that lead to mesenchymal-epithelial transition or MET exon 14 skipping).
Tabrecta is sponsored by Novartis.
FDA also approved the FoundationOne CDx assay (Foundation Medicine, Inc.) as a companion diagnostic for Tabrecta. Most patients had tumor samples that were tested for mutations that lead to MET exon 14 skipping using local tests and confirmed with the F1CDx, which is a next-generation sequencing based in vitro diagnostic device capable of detecting several mutations, including mutations that lead to MET exon 14 skipping.
“Lung cancer is increasingly being divided into multiple subsets of molecularly defined populations with drugs being developed to target these specific groups,” Richard Pazdur, director of the FDA Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement. “Tabrecta is the first approval specifically for the treatment of patients with non-small cell lung cancer whose tumors have mutations that lead to MET exon 14 skipping. This patient population now has an option for a targeted therapy, which they didn’t have prior to today.”
Efficacy was demonstrated in the GEOMETRY mono-1 trial (NCT02414139), a multicenter, non-randomized, open-label, multicohort study enrolling 97 patients with metastatic NSCLC with confirmed MET exon 14 skipping. Patients received Tabrecta 400 mg orally twice daily until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR) determined by a blinded independent review committee using RECIST 1.1 and response duration. Among the 28 treatment-naïve patients, the ORR was 68% (95% CI: 48, 84) with a response duration of 12.6 months (95% CI: 5.5, 25.3). Among the 69 previously treated patients, the ORR was 41% (95% CI: 29, 53) with a response duration of 9.7 months (95% CI: 5.5, 13.0).
