Novartis AG won accelerated FDA clearance for Tabrecta (capmatinib, formerly INC-280), an oral MET inhibitor, for adult patients with metastatic non-small-cell lung cancer (NSCLC) whose tumors have a mutation that leads to MET exon 14 skipping (METex14) as detected by a companion diagnostic, also given the green light.

Tabrecta was discovered by Wilmington, Del.-based Incyte Corp. and licensed to Novartis, of Basel, Switzerland, in 2009. Incyte granted Novartis exclusive worldwide development and commercialization rights to the drug and certain back-up compounds in all indications. The deal included more than $500 million in potential milestone payments as well as royalties of between 12% and 14% on global sales.

The kinase inhibitor’s approval “fills a long-recognized and urgent need” among METex14 patients who have not had a treatment option approved to target the driver of their lung cancer, Novartis said. Tabrecta is indicated for first-line and previously treated patients, regardless of prior treatment type, and is expected to become available to patients in the coming days, though pricing was not immediately disclosed. The companion diagnostic is Foundationone Cdx from Cambridge, Mass.-based Foundation Medicine Inc.

Regulators’ nod for breakthrough therapy-designated Tabrecta is based on results from the pivotal Geometry mono-1 phase II experiment. In the METex14 population (n=97), the confirmed overall response rate was 68% (95% confidence interval [CI], 48-84) and 41% (95% CI, 29-53) among treatment-naive (n=28) and previously treated patients (n=69), respectively, based on the blinded independent review committee assessment per RECIST v1.11.

In patients taking Tabrecta, the study also turned up a median duration of response of 12.6 months (95% CI, 5.5–25.3) in treatment-naive patients (19 responders). The number was 9.7 months (95% CI, 5.5-13) in previously treated patients (28 responders). The most common treatment-related adverse events (incidence ≥20%) were peripheral edema, nausea, fatigue, vomiting, dyspnea and decreased appetite.

NSCLC makes up about 85% of the 2 million new lung cancer diagnoses each year worldwide, including about 228,000 in the U.S., and almost 70% bear a genomic mutation. METex14 occurs in as much as 4% of newly diagnosed metastatic cases, or a range between 4,000 and 5,000 patients in the U.S. annually.

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