Policy & Regulation
Incyte Gains Acceptance and Priority Review of NDA for Capmatinib for Advanced Non-Small Cell Lung Cancer
12 February 2020 - - The US Food and Drug Administration has accepted and granted Priority Review to the New Drug Application for capmatinib, an investigational, selective MET inhibitor, as a treatment for first-line and previously treated patients with locally advanced or metastatic MET exon 14 skipping (METex14) mutated non-small cell lung cancer (NSCLC), US-based biopharmaceutical company Incyte (NASDAQ: INCY) said.

If approved, capmatinib will be the first therapy to specifically target METex14 mutated advanced lung cancer, a type of lung cancer with a particularly poor prognosis.

There are currently no approved therapies that specifically target METex14 mutated advanced NSCLC.

NSCLC accounts for approximately 85% of lung cancer diagnoses. METex14 mutations occur in 3-4% of newly-diagnosed advanced NSCLC cases5 and is a recognized oncogenic driver.

The FDA grants Priority Review to medicines that may offer a major advance in treatment where none currently exists. This designation shortens the FDA review period following the acceptance of the NDA to six months compared to 10 months for Standard Review. Capmatinib was previously granted Breakthrough Therapy designation by the FDA.

The NDA submission for capmatinib was supported by results from the Novartis-sponsored GEOMETRY mono-1 Phase 2 study, which demonstrated overall response rates of 67.9% (95% CI, 47.6 - 84.1) and 40.6% (95% CI, 28.9–53.1) among treatment-naïve and previously treated patients, respectively, based on the Blinded Independent Review Committee assessment per RECIST v1.1.

The study also demonstrated that capmatinib provided durable responses among all patients: median duration of response was 11.14 months (95% CI, 5.55 - NE) in treatment-naïve patients and 9.72 months (95% CI, 5.55 - 12.98) in previously treated patients.

All results were based on independent assessment by the BIRC, and all tumor CT scans were evaluated in parallel by two radiologists to confirm the response1.

The most common treatment-related adverse events (≥ 10% all grades) across all cohorts (N=334), were peripheral edema, nausea, creatinine increase, vomiting, fatigue, decreased appetite and diarrhea. The majority of the AEs were grades 1/21.

The Novartis-sponsored GEOMETRY mono-1 trial is an international, prospective, multi-cohort, non-randomized, open-label Phase 2 study to evaluate the efficacy and safety of single-agent capmatinib in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring a MET amplification and/or mutation. Patients with locally advanced or metastatic NSCLC harboring a MET exon-14 skipping mutation (centrally confirmed) were assigned to Cohorts 4 (previously treated patients) or 5B (treatment-naïve), regardless of MET amplification/gene copy number and received 400 mg capmatinib tablets orally twice daily.

The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was DOR by BIRC.

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor discovered by Incyte and licensed to Novartis in 2009.

Under the terms of the agreement, Incyte granted Novartis exclusive worldwide development and commercialisation rights to capmatinib and certain back-up compounds in all indications. If capmatinib is successfully developed by Novartis, Incyte may become eligible for over USD 500m in future milestones as well as royalties of between 12 and 14 % on global sales by Novartis.

Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics.