A phase II single-arm study of LDK378 in patients with ALK-activated (ALK+) non-small cell lung cancer (NSCLC) previously treated with chemotherapy and crizotinib (CRZ).

TPS8119 Background: NSCLC harboring anaplastic lymphoma kinase (ALK) gene rearrangements (2–8% of cases) are sensitive to CRZ, the only approved ALK inhibitor, but invariably develop resistance. There are currently no standard ALK-targeted treatments for CRZ-resistant ALK+ NSCLC. LDK378 is a novel, oral ALK inhibitor with 20-fold greater potency than CRZ in enzymatic assays. In an ongoing phase I trial, LDK378 has demonstrated substantial clinical activity in patients (pts) with ALK+ NSCLC whose disease has failed CRZ. At a dose ≥400 mg (45 pts), the overall response rate (ORR) was 80%, with 47% confirmed responses (data cutoff August 31, 2012). Nausea, vomiting, diarrhea and fatigue were the main toxicities. The recommended phase II dose is 750 mg daily. Methods: This phase II multicenter, open label, single-arm study (CLDK378A2201) is designed to evaluate the efficacy and safety of oral LDK378 750 mg once-daily in pts with ALK+ (by FDA-approved FISH test) advanced NSCLC. Pts must have received cytotoxic...