eXalt3: Phase III randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase positive non-small cell lung cancer patients

Abstract

Background: Ensartinib (X‐396) is a novel, potent ALK small molecule tyrosine kinase inhibitor (TKI). It is well‐tolerated and has shown promising activity in NSCLC patients in a phase 1/2 study in patients that were both ALK TKI naïve and patients that received prior crizotinib, as well as those with CNS metastases. The safety profile of ensartinib appears to be different from other ALK TKIs. Trial design: In this global, phase 3, open‐label, randomized study, approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized with stratification by prior chemotherapy (0/1), performance status (0‐1/2), brain metastases at screening (absence/presence), and geographic region (Asia /other), to receive oral ensartinib (225 mg, once daily) or crizotinib (250mg, twice daily) until disease progression or intolerable toxicity. Eligibility also 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 primary endpoint is progression‐free survival assessed by independent radiology review based on RECIST v. 1.1 criteria. 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. 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. Phase 3 recruitment began in June, 2016 and currently has 98 active sites in 21 countries. The duration of recruitment will be approximately 28 months.