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LUNG CANCER: FDA Grants Priority Review to NDA for Capmatinib in MET Exon 14+ NSCLC


Feb. 24, 2020


The FDA granted Priority Review to the New Drug Application (NDA) for capmatinib (INC280), an investigational selective MET inhibitor, which will be used as treatment for first-line and previously treated patients with locally advanced or metastatic MET exon 14 skipping-mutated non–small cell lung cancer (NSCLC), Incyte announced in a press release.

The NDA was backed by positive data from the phase II GEOMETRY mono-1 study of capmatinib monotherapy in adult patients EGFR-wildtype, ALK rearrangement–negative, advanced NSCLC harboring a MET amplification and/or mutation. An efficacy analysis of both treatment-naïve and previously treated patients showed a 67.9% overall response rate (ORR; 95% CI, 47.6%-84.1%) and a 40.6% ORR (95% CI, 28.9%-53.1%), respectively. The responses observed were also durable in both groups. The median duration of response (DOR) in treatment-naïve patients was 11.14 months (95% CI, 5.55-not evaluable) and was 9.72 months (95% CI, 5.55-12.98) in patients who were previously treated.

Per the safety analysis, the most common adverse events (AEs) were peripheral edema (42%), nausea (33%), creatinine increase (20%), vomiting (19%), fatigue (14%), decreased appetite (13%), and diarrhea (11%), with most being grade 1 or 2 in severity. Less than 10% of patients experienced an AE.

The international, prospective, multi-cohort, nonrandomized, open-label study (NCT02414139) continues to evaluate the safety and efficacy of single-agent capmatinib in this adult patient population. In the study, assigned to an arm based on whether they were treatment-naïve or previously treated and given oral capmatinib 400 mg twice daily.

The primary end point of the study is ORR with secondary end points including DOR, progression-free survival, and overall survival. 

Individuals with histologically or cytologically confirmed NSCLC that is EGFR-wildtype, ALK-negative, and with MET amplification are eligible to be included in the study. These patients were required to have an ECOG performance status of 0 or 1. The study excluded patients who had prior treatment with crizotinib or any other cMET or HGF inhibitors; characterized EGFR mutations that predict sensitivity to EGFR therapy; ALK rearrangements; clinically significant, uncontrolled heart diseases; received treatment with medications that cannot be discontinued at least 1 week prior to first dosing on the study; impairment of the gastrointestinal (GI) function or GI disease; and received treatment with any enzyme-inducing anticonvulsant.

If approved by the FDA, capmatinib will fill a gap in the treatment landscape for NSCLC, as no approved therapies currently exist that can specifically target MET exon 14–mutated advanced NSCLC, a mutation that occurs in 3% to 4% of newly diagnosed patients with NSCLC and is considered to be an oncogenic driver.   

“Patients with MET exon 14 mutated advanced NSCLC, an aggressive form of the disease, often face a poor prognosis due to lack of available treatment options,” said Steven Stein, MD, the chief medical officer of Incyte, in a statement. “We are pleased the FDA has accepted the NDA for capmatinib for Priority Review–a critical step toward providing the first MET exon 14 mutation targeted therapy to this subset of [patients with lung cancer].”