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FDA grants priority review to Zykadia for ALK–positive metastatic NSCLC
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The FDA granted priority review to a supplemental new drug application that seeks to expand the use of ceritinib to include first-line treatment of anaplastic lymphoma kinase–positive metastatic non–small cell lung cancer, according to the drug’s manufacturer.
Ceritinib (Zykadia, Novartis) — an oral, selective anaplastic lymphoma kinase (ALK) inhibitor — also received breakthrough therapy designation for the first-line treatment of patients with ALK–positive metastatic NSCLC with metastases to the brain.
The application included results from the randomized phase 3 ASCEND-4 trial, designed to compare the safety and efficacy of ceritinib with standard chemotherapy in 376 adults with stage IIIb or stage IV ALK–positive advanced NSCLC who received no prior therapy for their advanced disease.
Researchers assigned 189 study participants to 750 mg oral ceritinib. The other 187 received standard pemetrexed-based platinum doublet chemotherapy for four cycles, followed by pemetrexed maintenance. The study arms were balanced with regard to patients with brain metastases (ceritinib, n = 59; chemotherapy, n = 62).
Patients assigned ceritinib achieved superior median PFS (16.6 months vs. 8.1 months; HR = 0.55; 95% CI, 0.42-0.73).
Results showed ceritinib conferred a PFS benefit to patients without brain metastases (median, 26.3 months vs. 8.3 months; HR = 0.48; 95% CI, 0.33-0.69), as well as those with brain metastases (median, 10.7 months vs. 6.7 months; HR = 0.7; 95% CI, 0.44-1.12). Among those with brain metastases, intracranial overall response rate (72.7%) appeared consistent with whole-body overall response rate (72.5%).
The most common adverse events in the treatment group included diarrhea (85% for ceritinib vs. 11% for chemotherapy), nausea (69% vs. 55%), vomiting (66% vs. 36%), alanine transaminase increase (60% vs. 22%), aspartate transaminase (53% vs. 19%), gamma-glutamyl transferase increase (37% vs. 10%), decreased appetite (34% vs. 31%), blood alkaline phosphate increase (29% vs. 5%) and fatigue (29% vs. 30%).
“We are committed to advancing our understanding of mutation-driven lung cancer, where there continues to be significant unmet need,” Vas Narasimhan, global head of drug development and chief medical officer of Novartis, said in a company-issued press release. “[This] priority review of ceritinib for newly diagnosed patients with ALK-positive metastatic NSCLC, including breakthrough therapy designation for those with brain metastases, brings us closer to delivering the right treatment to the right patient at the right time.”