Novartis recently announced that the U.S. FDA has approved the targeted anticancer drug Tabrecta (capmatinib, formerly known as INC280) for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping (METex14) mutations, including both first-line treatment-naïve (treatment-naïve) and previously treated (treatment-experienced) patients.
Tabrecta is an oral, potent, selective MET inhibitor and the only FDA-approved therapy specifically targeting METex14-mutant metastatic NSCLC, regardless of prior treatment. In clinical trials, Tabrecta achieved an overall response rate (ORR) of 68% in treatment-naïve patients and 41% in previously treated patients with METex14 mutations. Tabrecta received approval through the accelerated approval process and priority review process based on its overall response rate (ORR) and duration of response (DOR). Continued approval for this indication will depend on the validation and description of clinical benefit in confirmatory trials.
This approval is based on positive results from the pivotal Phase II clinical trial GEOMETRY mono-1. This was an international, prospective, multi-cohort, non-randomized, open-label study conducted in 97 adult patients with locally advanced or metastatic NSCLC whose tumors contained MET exon 14 skipping (METex14) mutations. In the study, patients received Tabrecta 400 mg tablets orally twice daily.
Results showed that, as assessed by a double-blind independent review committee (BIRC) according to RECIST v1.1 (Responsive Evaluation Criteria for Solid Tumors), (1) in treatment-naïve patients (cohort 5b: 28 patients, previously untreated), the overall response rate (ORR) was 68% (95% CI: 48–84), and the median duration of response (DOR) was 12.6 months (95% CI: 5.5–25.3). (2) in treatment-experienced patients (cohort 4: 69 patients, previously treated), the ORR was 41% (95% CI: 29–53), and the DOR was 9.7 months (95% CI: 5.5–13.0). (3) The most common treatment-related adverse events included peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.
These results reveal the therapeutic potential of Tabrecta in patients with MET exon 14 skipping mutations in NSCLC. The superior ORR data in the treatment-naïve group compared to the previously treated group highlight the clinical relevance of early diagnostic testing and timely treatment in this highly challenging patient population.
METex14-mutant advanced NSCLC is a lung cancer with a very poor prognosis, and there is currently no definitive treatment for this aggressive lung cancer. In the United States, approximately 4,000–5,000 patients are diagnosed with METex14 metastatic NSCLC each year, and these patients have a very poor prognosis due to the presence of the METex14 mutation.
Tabrecta is expected to be available in the coming days, filling a long-standing unmet medical need in patients with METex14 mutations.
