eXalt3: A phase III study of ensartinib (X-396) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

TPS8578 Background: Ensartinib is a novel, potent anaplastic lymphoma kinase (ALK) small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. Ensartinib has demonstrated activity in ALK treatment naïve and previously treated patients and has a generally well tolerated safety profile. Methods: eXalt3 (NCT02767804) is a global, randomized, open-label phase III study comparing the efficacy and safety of ensartinib to crizotinib in ALK- positive TKI naïve non-small cell lung cancer (NSCLC) patients. It is being conducted in > 100 sites in North America, South America, Europe, and the Asia/Pacific region. Enrollment began in 2016. The primary efficacy endpoint is progression free survival (PFS) assessed by independent radiology review. Secondary efficacy endpoints include overall survival, response rates (overall and central nervous system [CNS]), PFS by investigator assessment, time to response, duration of response, and time to CNS progression. Approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized 1:1 to ensartinib 225 mg QD, or crizotinib 250 mg BID, with stratification based on prior chemotherapy, ECOG performance status (PS), CNS metastases and geographic region. Eligibility includes patients ≥ 18 years of age, stage IIIB or IV ALK+ NSCLC. Patients are required to have measurable disease per RECIST 1.1, adequate organ function, and an ECOG PS of ≤2. Adequate tumor tissue (archival or fresh biopsy) must be available for central testing. The study has > 80% power to detect a superior effect of ensartinib over crizotinib in PFS at a 2-sided alpha level of 0.05. Clinical trial information: NCT02767804.