Novartis announces MET inhibitor capmatinib, the first potential treatment for the METex14 mutated advanced non-small cell lung cancer, granted priority FDA review

Feb 11, 2020:  Novartis announced that the U.S.FDA accepted and granted Priority Review to capmatinib’s (INC280) NDA. Capmatinib is a MET inhibitor being evaluated as a treatment for the  first-line and formerly treated patients with locally advanced or metastatic MET exon 14 skipping (METex14) mutated non-small cell lung cancer (NSCLC). If accepted, capmatinib will be the first therapy to specially target METex14 mutated advanced lung cancer, a type of the lung cancer with a particularly poor prognosis.

Priority Review is granted to therapies that the FDA determines have the potential in order to provide considerable improvements in the treatment, diagnosis or prevention of the serious conditions. This designation shortens the FDA review period following the approval of the NDA to six months compared to ten months under Standard Review. Previously, Novartis granted Breakthrough Therapy designation for capmatinib.There are currently no approved therapies that especially target METex14 mutated advanced NSCLC. NSCLC accounts for about 85% of the lung cancer diagnoses. METex14 mutations occur in 3-4% of newly diagnosed superior NSCLC casesand is a recognized oncogenic driver.

The NDA submission for capmatinib is maintained by results from the GEOMETRY mono-1 Phase II study, which established an overall response rate of 67.9% (95% CI, 47.6 – 84.1) and 40.6% (95% CI, 28.9 – 53.1) among treatment-naïve and formerly treated patients, respectively, based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1. The study also demonstrated that the capmatinib provided durable responses among all the patients: median duration of response was 11.14 months (95% CI, 5.55 – NE) in the treatment-naïve patients and 9.72 months (95% CI, 5.55 – 12.98) in formerly treated patients.

All results were based on the independent appraisal by the BIRC, and all tumor CT scans were evaluated in parallel by two radiologistsin order to confirm the response. The most common treatment-related adverse events (AE) (≥ 10% all grades) across all the cohorts (N=334), were peripheral edema (42%), nausea (33%), creatinine increase (20%), vomiting (19%), fatigue (14%), decreased appetite (13%) and also diarrhea (11%).

Capmatinib (INC280) is an investigational, oral, active, and selective MET inhibitor that 
Incyte Corporation licensed to Novartis in 2009. Under the Agreement, Incyte has given 
exclusive development and marketing rights to capmatinib and certain back up compounds 
worldwide to Novartis in all indications.
https://www.novartis.com/news/media-releases/novartis-announces-met-inhibitor-capmatinib-inc280-first-potential-treatment-metex14-mutated-advanced-non-small-cell-lung-cancer-granted-priority-fda-review