ESMO Congress 2023 | OncologyPRO

Abstract 1370P

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

	Intracranial per RANO-BM (n=14)
Best objective response, n (%)
Complete response	2 (14.3)
Partial response	8 (57.1)
Stable disease	4 (28.6)
Progression disease	0
Not evaluable	0
Objective 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)

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.