Izalontamab brengitecan, or iza-bren, reduced the risk of disease progression or death by 59 percent against physician’s choice chemotherapy in patients with unresectable locally advanced, recurrent or metastatic hormone receptor-positive, HER2-negative breast cancer who had failed at least one prior line of chemotherapy, in the Phase 3 PANKU-Breast01 study presented at ESMO and published simultaneously in The Lancet. Median progression-free survival was 8.2 months on iza-bren (190 patients) against 4.0 months on chemotherapy (193 patients), a hazard ratio of 0.41 (95 percent confidence interval 0.33 to 0.53, p below 0.0001), at a median follow-up of 15.2 months.
The response data point the same way. Confirmed objective response was 40.5 percent on iza-bren against 20.2 percent on chemotherapy, and median duration of response was 6.9 months against 4.2 months. Overall survival, a key secondary endpoint, was immature at this prespecified interim analysis, and discontinuations for side effects were low in the reporting available. The enrolled population had progressed after endocrine therapy, CDK4/6 inhibition and taxane treatment, which makes it a later-line, treatment-resistant group rather than an early one.
Iza-bren is a bispecific antibody-drug conjugate targeting both EGFR and HER3, developed by Sichuan Biokin Pharmaceutical through its US arm SystImmune and licensed to Bristol Myers Squibb outside China. The companies say it has now shown clinical benefit in five distinct tumour types, and this is its second positive Phase 3 in breast cancer. Its companion lung study, PANKU-Lung01 in EGFR-mutated lung cancer after a third-generation EGFR inhibitor, is presented at ESMO on October 26.
The geographic limit is the open question, as with several of this week’s China-run registrational trials. PANKU-Breast01 ran in China, so global regulators will look to Bristol Myers’s own international trials for confirmation before the breast indication can travel.