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

Background

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.

Methods

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.

Results

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 1^st (1/14, 7%) or 2^nd (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: 1370P

Conclusions

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.

Clinical trial identification

NCT03753685.

Editorial acknowledgement

Medical writing assistance was funded by Betta Pharmaceuticals Co., Ltd.

Legal entity responsible for the study

The authors.

Funding

Betta Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.