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The FDA has granted Priority Review for the expanded use of ceritinib as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. The FDA also granted Breakthrough Therapy designation to ceritinib for the first-line treatment of patients with ALK+ metastatic NSCLC with metastases to the brain.

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The sNDA submission for first-line use of ceritinib is based on the primary analysis of ASCEND-4, a global phase III, randomized, open-label, multicenter clinical trial that evaluated safety and efficacy of ceritinib compared to platinum-based chemotherapy, including maintenance, in adult patients with stage IIIB or IV ALK+ NSCLC. The study was conducted at 134 clinical trial sites across 28 countries, and randomized across 376 patients. The study found the following:


* Patients treated with first-line ceritinib had a median progression-free survival (PFS) of 16.6 months (95% confidence interval [CI]: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance. A 45 percent risk reduction in PFS was obtained in the ceritinib arm compared to the chemotherapy arm (hazard ratio [HR] = 0.55, [95% CI: 0.42, 0.73; one-sided p value <0.001]).


* In a pre-specified analysis of patients receiving ceritinib without brain metastases at screening, patients experienced a median PFS of 26.3 months (95% CI: 15.4, 27.7), compared with 8.3 months (95% CI: 6.0, 13.7) among patients treated with chemotherapy (HR = 0.48 [95% CI: 0.33, 0.69]).


* In a pre-specified analysis of patients receiving ceritinib with brain metastases at baseline, the median PFS was 10.7 months (95% CI: 8.1, 16.4) in the ceritinib group versus 6.7 months (95% CI: 4.1, 10.6) in the chemotherapy group (HR = 0.70 [95% CI: 0.44, 1.12]). Intracranial overall response rate (ORR) (72.7%, [95% CI: 49.8, 89.3]) is consistent with whole body ORR (72.5% [95% CI: 65.5, 78.7]).



The most common adverse events occurring in more than 25 percent of ceritinib patients were diarrhea (85% vs. 11% with chemotherapy), nausea (69% vs. 55% with chemotherapy), vomiting (66% vs. 36% with chemotherapy), ALT increase (60% vs. 22% with chemotherapy), AST increase (53% vs. 19% with chemotherapy), gamma-glutamyl transferase increase (37% vs. 10% in chemotherapy), decreased appetite (34% vs. 31% with chemotherapy), blood alkaline phosphate increase (29% vs. 5% with chemotherapy), and fatigue (29% vs. 30% with chemotherapy).