The decision is based on primary findings from the phase II GEOMETRY mono-1 study (NCT02414139), in which capmatinib showed a 67.9% objective response rate (ORR; 95% CI, 47.6%-84.1%) by independent review (IR) in treatment-naive patients with METex14-altered NSCLC.
Novartis, the developer of the investigational, highly potent and selective MET inhibitor, stated in a press release that the regulatory filing for capmatinib with the FDA will take place in the fourth quarter of 2019.
"We are pleased to announce that the US Food and Drug Administration granted Breakthrough Therapy Designation to capmatinib as a first-line treatment for patients with metastatic MET exon14 skipping-mutated non–small cell lung cancer,” John Tsai, MD, head of Global Drug Development and chief medical officer, Novartis, stated in a press release.
Currently, no targeted therapies are approved to treat patients with METex14-mutated NSCLC. The mutations are identified in approximately 3% to 4% of all patients with NSCLC, and these patients typically have a poor prognosis.
Capmatinib is being examined across several cohorts of the GEOMETRY trial; cohorts 4 and 5b were presented at the 2019 ASCO Annual Meeting. Cohort 4 comprised pretreated patients with METex14 alterations in the second- or third-line setting (n = 69), while cohort 5b included treatment-naive patients (n = 28).
The median age across both cohorts was 71 years, and approximately 75% of patients had an ECOG performance status of 1. In cohort 4, 15.9% of patients had brain metastases versus 10.7% in cohort 5b. The most common prior therapy used was platinum-based chemotherapy (88.4%).
In pretreated patients, the ORR by IR with capmatinib was 40.6% (95% CI, 28.9%-53.1%). Moreover, the disease control rate (DCR) was 78.3% (95% CI, 66.7%-87.3%). The ORR by IR was 67.9% (95% CI, 47.6%-84.1%) for treatment-naïve patients, and the DCR was 96.4% (95% CI, 81.7%-99.9%).
Results also showed that the median duration of response by IR was 9.72 months in pretreated patients and 11.14 months in those who received the agent upfront. The median progression-free survival was 5.42 months in the pretreated group and 9.69 months for those treated in the frontline setting.
Approximately half of the patients with brain metastases at baseline experienced an intracranial response with capmatinib (7 of 13; 54%). Of these patients, 4 had a complete resolution of brain lesions (31%), and the intracranial DCR was 92.3% (12 of 13).
Patients who had prior therapy with crizotinib (Xalkori) or any other cMET or HGF inhibitor, have EGFR or ALK abnormalities, clinically significant or uncontrolled heart disease, had prior therapy with agents that cannot be discontinued ≥1 week prior to the first capmatinib treatment and for the duration of the study, impairment of gastrointestinal function or gastrointestinal disease, may receive treatment with any enzyme-inducing anticonvulsant, and a presence or history of interstitial lung disease or interstitial pneumonitis were excluded from enrollment in the trial.
Safety, which was assessed across all cohorts examined in the study, also included patients with MET dysregulated NSCLC (N = 334). Grade 3 treatment-related adverse events (TRAEs) occurred in 31.1% of patients and a grade 4 adverse event (AE) was seen in 4.5% of patients.
The most common grade 3/4 AEs were peripheral edema (7.5%) and fatigue (3.0%). The most common all-grade treatment-related AEs were peripheral edema (41.6%), nausea (33.2%), increased blood creatinine (19.5%), and vomiting (18.9%).
“As we continue to reimagine medicine and place a renewed focus on the development of innovative lung cancer treatments, we look forward to working with the FDA and global health authorities to bring capmatinib to patients who currently have no available targeted therapy options,” Tsai concluded in the press release.
The FDA previously granted capmatinib an orphan drug designation and also a breakthrough therapy designation for patients with METex14 skipping mutation–positive metastatic NSCLC following platinum-based chemotherapy.
This article originally appeared on OncLive as, “FDA Grants Capmatinib Breakthrough Designation in Frontline METex14-Mutated NSCLC”
- Novartis investigational lung cancer therapy capmatinib (INC280) granted FDA Breakthrough Therapy Designation for patients with MET-mutated advanced non-small cell lung cancer[news release]. Basel, Switzerland: Novartis. Published September 6, 2019. https://bit.ly/2lCvaSy. Accessed September 6, 2019.
- Wolf J, Setons T, Han J-Y, et al. Capmatinib (INC280) in METΔex14-mutated advanced non-small cell lung cancer (NSCLC): efficacy data from the phase II GEOMETRY mono-1 study. J Clin Oncol. 2019;37(suppl; abstr 9004). doi: 10.1200/JCO.2019.37.15_suppl.9004.