WASHINGTON — The FDA approved the kinase inhibitor capmatinib (Tabrecta) to treat adult patients with metastatic non-small cell lung cancer (NSCLC) with specific tumor mutations.
While 90% of all lung carcinomas are NSCLC, roughly 3-4% of lung cancer patients have mutations that lead to mesenchymal-epithelial transition (MET) exon 14 skipping, which is “recognized as a critical event for metastasis of carcinomas,” the FDA explained. Capmatinib — which received Accelerated Approval, Breakthrough Therapy, Priority Review, and Orphan Drug designations — is the first targeted therapy for this patient population.
In addition to the new drug, the FDA also approved the FoundationOne CDx (F1CDx), a “next-generation sequencing based in vitro diagnostic device that is capable of detecting several mutations, including mutations that lead to MET exon 14 skipping,” the agency added.
“Lung cancer is increasingly being divided into multiple subsets of molecularly defined populations with drugs being developed to target these specific groups,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a statement. “[Capmatinib] is the first approval specifically for the treatment of patients with non-small cell lung cancer whose tumors have mutations that lead to MET exon 14 skipping. This patient population now has an option for a targeted therapy, which they didn’t have prior to today.”
This approval was based on the results of a multicenter, non-randomized, open-label, multi-cohort study of 97 patients with NSCLC with a mutation leading to MET exon 14 skipping, epidermal growth factor receptor (EGFR) wild-type and anaplastic lymphoma kinase (ALK) negative status, and at least one measurable lesion.
“During the clinical trial, participants received [capmatinib] 400 mg orally twice daily until disease progression or unacceptable toxicity,” the FDA wrote. “The major efficacy outcome measure was overall response rate (ORR)… An additional efficacy outcome measure was duration of response (DOR). The efficacy population included 28 patients who had never undergone treatment for NSCLC and 69 previously treated patients. The ORR for the 28 participants was 68%, with 4% having a complete response and 64% having a partial response. The ORR for the 69 participants was 41%, with all having a partial response. Of the responding participants who had never undergone treatment for NSCLC, 47% had a duration of response lasting 12 months or longer compared to 32.1% of the responding participants who had been previously treated.”
The FDA noted several side effects in patients taking capmatinib, including peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite. In addition, they warned that the drug can occasionally lead to more severe side effects, including interstitial lung disease or pneumonitis. “[Capmatinib] should be permanently discontinued in patients with these side effects. [Capmatinib] may also cause hepatotoxicity, and health care professionals should monitor a patient’s liver function tests prior to starting and when taking [capmatinib]. If a patient experiences hepatotoxicity, [capmatinib] should be withheld, dose reduced, or permanently discontinued. Based on a clear positive signal for phototoxicity in laboratory studies in cells, patients may be more sensitive to sunlight and should be advised to take precautions to cover their skin and use sunscreen and not to tan while taking [capmatinib].”
The FDA also warned that the drug can cause harm to a developing fetus or newborn and advised health care professionals to discuss this risk with pregnant women. The agency also suggested that physicians “should advise both females of reproductive potential and male patients with female partners of reproductive potential to use effective contraception during treatment with [capmatinib] and for one week after the last dose.”
Capmatinib is manufactured by Novartis Pharmaceuticals Corporation; the F1CDx companion diagnostic is manufactured by Foundation Medicine, Inc.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 24
Topic ID: 78,24,730,24,192,65