Iruplinalkib (WX-0593) is an orally active, selective and potent ALK and ROS1 tyrosine kinase inhibitor with anticancer activity for use in the study of non-small cell lung cancer.

METHODS: In this open-label, randomized, multicenter, phase 3 study, patients with ALK-positive NSCLC were randomized to receive iruplinalkib 180 mg once daily (7 days, 60 mg once daily) or crizotinib 250 mg twice daily. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC) according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included PFS by investigator, objective response rate (ORR), duration of response, duration of response, intracranial ORR and time to CNS progression by IRC and investigator, overall survival, and safety. An interim analysis was planned after approximately 70% of all 192 expected PFS events assessed by IRC were observed (134 events).
RESULTS: Between September 4, 2019, and December 2, 2020, a total of 292 patients were randomized; 143 to iruplinalkib and 149 to crizotinib. At this interim analysis (145 events), the median follow-up was 26.7 months (range: 3.7-37.7) in the iruplinalkib group and 25.9 months (range: 0.5-35.9) in the crizotinib group. IRC-assessed PFS was significantly prolonged in patients in the iruplinalkib group (median PFS, 27.7 months [95% confidence interval (CI): 26.3-not estimable], vs. 14.6 months [95% CI: 11.1-16.5] in the crizotinib group; hazard ratio, 0.34 [98.02% CI: 0.23-0.52], p < 0.0001). IRC-assessed ORR was 93.0% (95% CI: 87.5-96.6) in the iruplinalkib group and 89.3% (95% CI: 83.1-93.7) in the crizotinib group. For patients with measurable CNS metastases at baseline, the intracranial ORR was 90.9% with iruplinalkib (10 of 11 patients, 95% CI: 58.7-99.8) and 60.0% with crizotinib (9 of 15 patients, 95% CI: 32.3-83.7). The incidence of grade 3 or 4 treatment-related adverse events was 51.7% with iruplinalkib and 49.7% with crizotinib.[1]