MINI01.02: Response and Plasma Genotyping from Phase I/II Trial of Ensartinib (X-396) in Patients (pts) with ALK+ NSCLC: Topic: Medical Oncology.

Ensartinib (X-396) 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. We report data on the ALK TKI-naïve and crizotinib (C)-resistant NSCLC pts treated with ensartinib. Clinical trial information: NCT01625234 In this multicenter expansion study, pts with ALK+ NSCLC were treated with ensartinib 225 mg daily on a 28-day schedule. Pts had measurable disease, ECOG PS 0-1, and adequate organ function. Untreated brain metastases (CNS) and leptomeningeal disease were allowed. Next Generation Sequencing (NGS) was performed on plasma samples collected at baseline and on study and compared with central tissue results (FISH/IHC). All pts were assessed for response to therapy using RECIST 1.1 and for adverse events (AEs) using CTCAE version 4.03. 83 pts (51% female) have been enrolled. Median age 54 (20-79) years, 64% ECOG PS 1. Of 42 ALK+ NSCLC pts evaluable for response; partial response (PR) was achieved in 25 pts (60%) and stable disease (SD) in 6 pts (14%). In the C-naïve pts (n = 9), PRs were observed in 7 pts (77%). In the 22 pts with prior C but no other ALK TKI, 16 pts (73%) achieved PR and 4 (18%) SD. In the 10 pts who had received two or more prior ALK TKIs, there were 2 PR, 2 SD (40% DCR). CNS responses (53% PR) have been observed in both C-naïve and C-resistant pts. Plasma and tissue genotyping were available on 27 pts (26 ALK+ and 1 ALK-). ALK was detected in plasma in 16 pts, all of whom had a response to therapy. 2 pts with PD were tissue +ve and plasma -ve. 9 plasma samples were unevaluable. Serial sequencing demonstrated a decrease in ALK in pts responding and an increase at the time of progression. The most common drug-related AEs (≥ 20% of pts) included rash (53%), nausea (33%), vomiting (27%), fatigue (22%), and pruritus (23%). Most AEs were Grade (G) 1-2. The G3 treatment-related AEs in ≥2 pts were rash (9 pts), pruritus (3 pts), and fatigue (2 pts). Ensartinib is generally well-tolerated and induces response in both C-naïve and C-resistant ALK+ NSCLC pts, as well as pts with CNS disease. Plasma sequencing appears to be promising to select pts for therapy and monitor for response and development of resistance.