Izalontamab brengitecan cuts progression risk by 59% in HR+/HER2- breast cancer

SystImmune and Bristol Myers Squibb announced that their investigational bispecific antibody-drug conjugate izalontamab brengitecan, also called iza-bren, met its primary endpoint in the Phase 3 PANKU-Breast01 trial, reducing the risk of disease progression or death by 59% compared with chemotherapy in patients with advanced hormone receptor-positive, HER2-negative breast cancer. The results were reported during a late-breaking oral presentation at the European Society for Medical Oncology Congress 2026 in Madrid and were published simultaneously in The Lancet.

In the open-label trial, 383 patients at 72 centers in China were randomized to receive iza-bren 2.5 mg/kg on days 1 and 8 of each 21-day cycle or physician's choice chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine. The enrolled population had unresectable, locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer and had progressed after at least one endocrine therapy, a CDK4/6 inhibitor, a taxane, and one or two prior chemotherapy regimens.

After a median progression-free survival follow-up of 15.2 months, blinded independent central review showed a median progression-free survival of 8.2 months for iza-bren (n=190) compared with 4.0 months for chemotherapy (n=193), yielding a hazard ratio of 0.41 (95% CI 0.33–0.53; p<0.0001). Confirmed objective response rate was 40.5% versus 20.2%, and median duration of response was 6.9 months versus 4.2 months. Overall survival, a key secondary endpoint, was immature at the prespecified interim analysis.

Regarding safety, treatment-related grade 3 or higher adverse events were observed in 85.3% of patients on iza-bren versus 65.8% on chemotherapy; the most common events were anemia, thrombocytopenia, leukopenia, and neutropenia. Dose reductions were needed in 64.7% of the iza-bren group versus 28.5% of the chemotherapy group, but permanent discontinuation due to treatment-related adverse events was rare (1.6% vs 1.0%). SystImmune and Bristol Myers Squibb described the safety profile as manageable with no new safety signals; adjudicated interstitial lung disease occurred in two iza-bren patients (1.1%), both grade 1 or 2. Treatment-related deaths were reported in two patients on iza-bren (1.1%) and one on chemotherapy (0.5%).

Professor Binghe Xu of the Cancer Hospital Chinese Academy of Medical Sciences said in the press release that the trial "provides encouraging evidence for a new therapeutic approach". OncoDaily, which reported the presentation, noted that the study was conducted entirely in China and that the comparator was chemotherapy rather than another antibody-drug conjugate, so the results do not establish how iza-bren compares with other ADC therapies in this setting. The report also said global generalizability remains an important limitation because treatment patterns and sequencing of ADCs can differ across regions.

Outside China, iza-bren is co-developed by SystImmune and Bristol Myers Squibb through a license agreement; the PANKU-Breast01 trial is sponsored by SystImmune's parent, Sichuan Biokin Pharmaceutical, in mainland China. The companies stated that iza-bren has shown clinical activity in five Phase 3 trials across five cancer types, including previously treated HR-positive/HER2-negative breast cancer, previously treated EGFR-mutant non-small cell lung cancer, nasopharyngeal carcinoma after prior therapy, previously treated esophageal squamous cell carcinoma, and advanced triple-negative breast cancer.