Real-world data on the efficacy and safety of iruplinalkib (WX-0593) in ALK-positive advanced lung adenocarcinoma patients previously treated with lorlatinib.

Abstract

8638 Background: Iruplinalkib (WX-0593) is a novel anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI). Here we report the results from a retrospective observational study on efficacy and safety of iruplinalkib in ALK-positive lung adenocarcinoma (LUAD) patients who had previous treatment with lorlatinib. Methods: Patients with ALK-positive advanced LUAD who either experienced disease progression on or were intolerant to lorlatinib were evaluated for clinical outcomes including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profiles. Results: A total of 11 patients were enrolled in this study, of which five (45%) were male, eight (73%) experienced treatment failure with lorlatinib, and seven (64%) received prior two or more second-generation TKIs. The median age was 49-years old. All patients received 180 mg of iruplinalkib orally daily. The median treatment line with iruplinalkib was six. Brain metastasis and prior treatment were summarized in the table. As of the data cut-off date on December 31, 2024, the median follow-up was 8.1 months. The ORR was 27%, and the DCR was 91%. The 12-month PFS rate was 53.0%, while the median PFS and OS were not reached. Eight (73%) and one (9%) patient experienced any grade and grade ≥ 3 treatment-related adverse event (TRAE), respectively. Conclusions: Iruplinalkib exhibited promising efficacy and acceptable toxicity in patients with ALK-positive advanced LUAD patients who were previously treated with lorlatinib. Parameters Results (n=11) Baseline brain metastasis 9 (82%) Prior ALK TKIs Crizotinib + second-generation + lorlatinib 10 (91%) Second-generation + lorlatinib 1 (9%) Detailed second-generation ALK TKI Aletinib 8 (73%) Ceritinib 6 (55%) Brigatinib 3 (27%) Ensartinib 3 (27%) Prior chemotherapy 5 (45%) Prior anti-angiogenesis 8 (73%) Prior immune checkpoint inhibitor 2 (18%) Best objective response Partial response 3 (27%) Stable disease 7 (64%) Progressive disease 1 (9%) Objective response 3 (27%) Disease control 10 (91%） PFS event 3 (27%) 12m PFS rate 53.0% Median PFS, months NR Any grade TRAE 8 (73%) Grade ≥ 3 TRAE 1 (9%) TRAE leading to dose interruption/reduction/discontinuation 1 (9%) /0/0