Real-world efficacy and safety of iruplinalkib in <i>ALK</i> -positive advanced lung adenocarcinoma patients previously treated with lorlatinib.

Abstract

e20730 Background: Treatment options after lorlatinib failure remain limited in patients with anaplastic lymphoma kinase ( ALK )-positive advanced lung adenocarcinoma (LUAD). Iruplinalkib (WX-0593) has shown systemic and intracranial activity. We report updated results with extended follow-up from a real-world study evaluating iruplinalkib in this setting. Methods: Patients with ALK -positive advanced LUAD who received iruplinalkib after progression on or intolerance to lorlatinib were included. The primary endpoint was real-world progression-free survival (rwPFS). Secondary endpoints included real-world objective response rate (rwORR), disease control rate (rwDCR), overall survival (OS), and safety. Data cutoff was December 31, 2025 (ChiCTR2600116971). Results: Sixteen heavily pretreated patients were included, with a median of 4 prior systemic therapy lines (range 2–7); 81.3% (13/16) had baseline brain metastases. Iruplinalkib was administered as monotherapy in 62.5% of patients , while 37.5% received combination therapies based on physician discretion. With a median follow-up of 15.8 months, the rwORR was 31.3% (5/16) and rwDCR was 87.5% (14/16). The median PFS was 12.4 months (95% CI: 7.66–NE). The median OS reached 22.1 months (95% CI: 22.1–NE), although OS data remain immature. Safety profiles were consistent with previous reports. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 12.5% of patients, with no new safety signals observed. Conclusions: In this updated analysis, iruplinalkib demonstrated durable clinical efficacy in heavily pretreated ALK -positive LUAD patients progressing on lorlatinib, including those with a high burden of brain metastases. The median PFS of 12.4 months and OS of 22.1 months in a ≥ 4 th -line setting supports iruplinalkib as a promising salvage option. Clinical trial information: ChiCTR2600116971. Baseline characteristics and clinical outcomes. Parameters Results (N=16) Baseline Characteristics Age (median, range) 48.5 (34.00-63.00) Sex Male 6 (37.5%) Female 10 (62.5%) ECOG PS 0-1 12 (75.0%) ≥2 4 (25.0%) Baseline brain metastasis 13 (81.3%) Prior ALK TKIs Crizotinib + 2nd-generation TKIs + lorlatinib 13 (81.3%) 2nd-generation TKIs + lorlatinib 3 (18.8%) Prior 2nd-generation ALK TKI Aletinib 12 (75.0%) Ceritinib 6 (37.5%) Brigatinib 4 (25.0%) Ensartinib 5 (31.3%) Other Prior Therapies Prior chemotherapy 9 (56.3%) Prior anti-angiogenesis 10 (62.5%) Prior immune checkpoint inhibitor 2 (12.5%) Efficacy Partial response 5 (31.3%) Stable disease 9 (56.3%) Progressive disease 1 (6.3%) Not evaluated 1 (6.3%) Objective response rate (ORR) 31.3% (5/16) Disease control rate (DCR) 87.5% (14/16) Median PFS (95% CI) 12.4 months (7.66–NE) Median OS (95% CI) 22.1 months (22.1–NE) Safety Any grade TRAE 9 (56.3%) Grade ≥ 3 TRAE 2 (12.5%) TRAE leading to dose interruption/reduction/discontinuation 1 (6.3%) /0/0