1370P Efficacy and safety of ensartinib in ALK-positive non-small cell lung cancer patients with brain metastases: A multicenter, open-label, single-arm, phase II study

Brain metastases (BM) are a major cause of mortality in patients (pts) with ALK-positive (ALK+) non–small cell lung cancer (NSCLC). Here, we evaluated efficacy and safety of ensartinib, an ALK-TKI, in ALK+ NSCLC pts with BM. This ongoing, multicenter, open-label phase 2 study enrolled locally advanced/recurrent/metastatic ALK+ NSCLC pts with BM, having ≤1 prior chemotherapy. Eligible pts were brain-enhanced MRI/CT-confirmed BM without CNS metastasis (except clinically stable)/risk of cerebral hemorrhage, and with ≥1 measurable intracranial lesion having no radiotherapy based on Response Assessment in Neuro-oncology BM (RANO-BM). Pts received 225 mg ensartinib orally once daily. Primary endpoint was intracranial objective response rate (iORR) by RANO-BM. As of Mar 24, 2023, 17 pts were enrolled. 14 pts who had ≥1 efficacy assessment were included in efficacy/safety analysis. Pts received ensartinib as 1st (1/14, 7%) or 2nd (13/14, 93%) -line therapy (with prior crizotinib). The iORR was 71.4% (10/14; 95% CI, 41.9%-91.6%), with median intracranial duration of response of 13.01 months (Table). The intracranial disease control rate and median intracranial progression-free survival (iPFS) were 100.0% and 13.63 months. Median PFS was 13.63 months. Overall survival was immature. Median cerebrospinal fluid/plasma concentration ratio was 1.52% in 10 pts, consistent with reported in phase Ⅰ study of ensartinib. No mini mental status examination decline (>3 from baseline) events observed. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 28.6% pts, with no grade 5 TRAEs/deaths. Most common TRAE was rash (85.7%).Table: 1370PIntracranial per RANO-BM (n=14)Best objective response, n (%)Complete response2 (14.3)Partial response8 (57.1)Stable disease4 (28.6)Progression disease0Not evaluable0Objective response rate, % (95% CI)71.4 (41.9, 91.6)Disease control rate, % (95% CI)100 (76.8, 100.0)Time to progression, months (95% CI)13.63 (4.44, not evaluable)Duration of response, months (95% CI)13.01 (5.42, not evaluable)Progression-free survival, months (95% CI)13.63 (4.44, not evaluable) Open table in a new tab Ensartinib showed promising intracranial efficacy with high blood-brain barrier penetration and a tolerable safety profile in ALK+ NSCLC pts with BM. Study is ongoing and final results will be presented in future.