Phase 1/2 Study of Ensartinib and Durvalumab, in ALK-rearranged Non-small Cell Lung Cancer

Prior to initiation of combination therapy with ensartinib plus durvalumab, subjects were enrolled sequentially to receive ensartinib monotherapy (orally once daily) during a pre-immunotherapy Run-in Period for one to two 28-day cycles. The purpose of the Run-in Period was to determine whether any safety signals might compromise combination therapy and to determine the effect of ALK inhibitor therapy on the immune tumor microenvironment. For subjects with no dose-limiting toxicity (DLT) during the Run-in Period, combination therapy was then initiated during a dose-finding phase using a standard 3 + 3 design until determination of the RCD, which was defined as the highest dose level at which ≤ 1 of 6 subjects (i.e., \< 33%) experienced DLTs during the first 2 cycles of combination treatment. A fixed dose of durvalumab (1500 mg by intravenous \[IV\] infusion every 4 weeks) was administered in all cohorts. Ensartinib dosing started at 200 mg, with subsequent cohorts receiving a reduced (150 mg) or escalated (225 mg) ensartinib dose depending upon observed toxicity. The study was then designed to include an expansion phase, in which the RCD cohort would be expanded to a total of 20 subjects. Subjects were monitored for safety (including immune-related adverse events), disease status (using the Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1 and immune-related RECIST), and biologic activity (peripheral blood assays and immunological changes in the tumor microenvironment) for the duration of study participation.