FDA Grants Regular Approval to Capmatinib for Patients With METex14-Positive NSCLC

An accelerated approval by the FDA for capmatinib has be converted to a regular approval based on new data from adults patients with metastatic non–small cell lung cancer whose tumors have a mutation leading to MET exon 14 skipping.

Regular FDA approval has been granted to capmatinib (Tabrecta) for adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation leading to MET exon 14 skipping, as detected by an FDA-approved test.1

This decision follows an accelerated approval for capmatinib in May of 2022 based on initial findings from the phase 2 GEOMETRY mono-1 trial (NCT02414139). In the study, a positive overall response rate in patients with metastatic non–small cell lung cancer with MET exon 14 skipping in their tumors. The agent also demonstrated good response durability.

The ORR initially observed with capmatinib in the treatment-naïve population was 67.9% (95% CI, 47.6%-84.1%). In patients with pretreated disease the ORR was 40.6% (95% CI, 28.9%-53.1%). The disease control rate (DCR) in the treatment-naïve was 78.3% (95% CI, 66.7%-87.3%). In the pretreated population, the DCR was 96.4% (95% CI, 81.7%-99.9%).2

Adverse events (AEs) occurred in ≥ 20% of patients in the study. The most frequently reported treatment-related AEs were peripheral edema (43%), nausea (34%), increased blood creatinine (18%), and vomiting (19%). Most of the events reported were grades 1 and 2.

The accelerated approval was changed to a regular approval as a result of results from an additional 63 patients in the study who were followed for an additional 22 months. With further follow-up, the study investigators assess duration of response (DOR), and the clinical benefit rate.1

In 60 treatment-naive patients, the ORR 68% (95% CI: 55, 80) with a 16.6-month DOR (95% CI: 8.4, 22.1). In the previously-treated population, the ORR was 44% (95% CI: 34, 54) with a 9.7-month DOR (95% CI: 5.6, 13).

For safety, the most common adverse reactions (≥ 20%) in the additional 63 patients were edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased appetite.

The prospective, international, open-label, multiple-cohort, phase 2 GEOMETRY mono-1 study was launched based on preclinical evidence that single-agent capmatinib is effective for MET-dysregulated NSCLC. In the study, patients with advanced NSCLC with MET exon 14 skipping mutation or MET amplification with or without prior treatment were enrolled. The primary end point of the study was ORR, and the secondary end points were DOR, time to response, disease control, progression-free survival (PFS), safety, and pharmacokinetics.

The study initially enrolled 364 patients with advanced NSCLC, and 97 of them had MET exon 14 skipping, while the remaining 210 had MET amplification. The patients were divided into 7 cohorts. In cohorts 1 through 4, patients were previously treated with up to 2 prior lines of therapy. In cohorts 5a and 5b, patients were treatment naïve. Patients in cohort 6 were those with MET amplifications who had received one prior line of therapy, and cohort 7 was compiled of patients MET exon 14 skipping mutation who were treatment naïve.


1. FDA approves capmatinib for metastatic non-small cell lung cancer. News release.FDA. August 10, 2022. Accessed August 11, 2022. https://bit.ly/3Pi05M4

2. Novartis announces NEJM publication of pivotal study of Tabrecta™ in patients with METex14 metastatic non-small cell lung cancer. News release. Novartis. September 2, 2020. Accessed August 11, 2022. https://bit.ly/2Z4sRZq