Izalontamab brengitecan, or iza-bren, doubled median progression-free survival against platinum-based chemotherapy in patients with EGFR-mutated non-squamous non-small cell lung cancer previously treated with an EGFR tyrosine kinase inhibitor, in the Phase 3 PANKU-Lung01 study presented at ESMO on October 26 and published simultaneously in The Lancet. Median progression-free survival by blinded independent central review was 11.1 months on iza-bren (216 patients) against 5.7 months on chemotherapy (206 patients), a hazard ratio of 0.40 (95 percent confidence interval 0.31 to 0.51, p below 0.0001), at a median follow-up of 14.6 months. The confirmed response rate was 60.2 percent against 34.5 percent, and median duration of response was 10.4 months against 5.7 months.
Overall survival, a secondary endpoint, was immature at this prespecified interim analysis, though the companies reported a favourable trend for iza-bren. On safety, grade 3 or higher treatment-related adverse events were predominantly blood-related, only 1.9 percent of iza-bren patients discontinued for treatment-related events, and adjudicated interstitial lung disease was uncommon, two patients, 0.9 percent, one grade 3 and one grade 1. The companies reported no new safety signals.
The setting is the same resistance problem addressed by AstraZeneca’s SAFFRON result this weekend, approached differently. Where SAFFRON adds a MET inhibitor for the biomarker-selected third of patients with MET-driven resistance, iza-bren, an EGFR by HER3 bispecific antibody-drug conjugate, is being tested without that selection step. Investigator Li Zhang of Sun Yat-sen University Cancer Center said the findings suggest iza-bren could change the trajectory of the disease after EGFR inhibitor failure, where chemotherapy has been the default.
The geographic caveat from yesterday’s breast cancer result applies unchanged. PANKU-Lung01 is a China-run registrational trial from Sichuan Biokin, SystImmune’s parent, with Bristol Myers holding rights outside China. Two positive Phase 3 trials in one weekend make iza-bren a platform claim rather than a single-indication one, and Bristol Myers’s international trials are what will decide whether that claim travels.