FDA Grants Accelerated Approval to Capmatinib for Metastatic Non-Small Cell Lung Cancer
On May 6, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-capmatinib-metastatic-non-small-cell-lung-cancer) to capmatinib (Tabrecta™) for adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping, as detected by an FDA-approved test. It is the first drug approval (https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-aggressive-form-lung-cancer) for this specific patient population and the first targeted therapy for the indication.
FDA also approved the FoundationOne®CDx assay as a companion diagnostic for capmatinib.
Efficacy was demonstrated in a multicenter, nonrandomized, open-label, multicohort study (GEOMETRY mono-1 trial; NCT02414139) enrolling 97 patients with metastatic NSCLC and confirmed MET exon 14 skipping. Patients received capmatinib (400 mg orally twice daily) until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR), determined by a blinded independent review committee using response evaluation criteria in solid tumors 1.1, and response duration. Among the 28 treatment-naïve patients, ORR was 68% (95% CI = 48, 84) with a response duration of 12.6 months (95% CI = 5.5, 25.3). Among the 69 previously treated patients, ORR was 41% (95% CI = 29, 53) with a response duration of 9.7 months (95% CI =5.5, 13.0).
The most common adverse reactions (≥ 20%) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite. Capmatinib can also cause interstitial lung disease, hepatotoxicity, photosensitivity, and embryo-fetal toxicity. Based on a clear positive signal for cell phototoxicity in early laboratory studies, patients may be more sensitive to sunlight and should be advised to take precautions to cover their skin, use sunscreen, and not tan while taking capmatinib.
The recommended capmatinib dose is 400 mg orally twice daily with or without food.
The indication received accelerated approval based on ORR and response duration. Continued approval for this indication may be contingent on verification and description of clinical benefit in confirmatory trials.
The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved this application three months ahead of its goal date.
FDA granted capmatinib orphan drug and breakthrough therapy designations. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).