FDA Grants Priority Review to Ceritinib for First-line Treatment of ALK+ NSCLC
The U.S. FDA granted Breakthrough Therapy designation to ceritinib for first-line treatment of ALK-positive NSCLC with metastases to the brain.
The US Food and Drug Administration (FDA) has granted Priority Review to the supplemental New Drug Application (sNDA) for the expanded use of ceritinib as a first-line treatment for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).1
The FDA also granted Breakthrough Therapy designation to ceritinib for the first-line treatment of patients with ALK-positive metastatic NSCLC with metastases to the brain.
The sNDA is based on data from the primary analysis of the international, open-label, phase 3 ASCEND-4 trial, which evaluated the efficacy and safety of ceritinib compared with platinum-based chemotherapy in 376 patients with stage IIIB or IV ALK-positive NSCLC.
Treatment with ceritinib significantly reduced the risk of progression or death by 45% compared with standard first-line pemetrexed plus platinum chemotherapy followed by pemetrexed maintenance (hazard ratio [HR], 0.55; 95% CI, 0.42-0.73; P <.001); median progression-free survival was 16.6 months (95% CI, 12.6-27.2) and 8.1 months (95% CI, 5.8-11.1), respectively.
Among patients with brain metastases, median progression-free survival was 10.7 months (95% CI, 8.1-16.4) with ceritinib vs 6.7 months (95% CI, 4.1-10.6) with chemotherapy (HR, 0.70; 95% CI, 0.44-1.12). Nearly three-quarters of patients (72.7%; 95% CI, 49.8-89.3) achieved an intracranial response, which was consistent with the whole body overall response rate of 72.5% (95% CI, 65.5-78.7).
The most common adverse events in the ceritinib group were diarrhea, nausea, vomiting, ALT elevation, AST elevation, GGT increase, decreased appetite, alkaline phosphatase elevation, and fatigue.
The FDA is expected to take action on this application by June 22, 2017. If approved, ceritinib would be the second targeted therapeutic option approved for previously untreated patients with ALK-positive metastatic NSCLC.
Ceritinib is a kinase inhibitor currently indicated for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib.
1. Novartis drug Zykadia receives FDA Priority Review for first-line use in patients with ALK+ metastatic NSCLC [news release]. Basel, Switzerland: Novartis; February 23, 2017.