REDMOND, Wash. & PRINCETON, N.J., February 26, 2026
SystImmune, Inc. and Bristol Myers Squibb announced positive interim topline results from a Phase III clinical trial evaluating izalontamab brengitecan (iza-bren) in patients with previously treated unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). The investigational therapy met its dual primary endpoints of progression-free survival (PFS) and overall survival (OS) in a pre-specified interim analysis, marking a significant milestone in the development of bispecific antibody-drug conjugates (ADCs) for aggressive breast cancers.
Dual PFS and OS Endpoints Achieved in Phase III
The Phase III study (BL-B01D1-307; NCT06382142), conducted in China, evaluated iza-bren in TNBC patients whose disease progressed following prior taxane therapy. According to topline findings, iza-bren demonstrated statistically significant and clinically meaningful improvements in both PFS and OS compared to chemotherapy of physician’s choice, successfully meeting both primary endpoints at interim analysis. This study represents the third Phase III trial in which iza-bren has achieved its primary endpoint(s), reinforcing the robustness of its clinical development program.
Importantly, iza-bren is reported as the first bispecific antibody-drug conjugate to demonstrate dual positive PFS and OS results in a Phase III TNBC trial, underscoring its potential to reshape treatment paradigms in a cancer subtype characterized by poor prognosis and limited targeted therapy options. Patients with advanced TNBC who progress after standard regimens often face aggressive disease progression and short survival durations, highlighting the urgent need for more effective therapies.
Bispecific ADC Innovation Targeting EGFR and HER3
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Iza-bren (BL-B01D1) is an investigational EGFR×HER3 bispecific antibody-drug conjugate, designed to simultaneously target two well-established oncogenic drivers highly expressed in epithelial tumors. By blocking both EGFR and HER3 signaling pathways, the therapy reduces tumor cell proliferation and survival signals. Upon internalization, its novel topoisomerase I inhibitor (Topo1i) payload is released, inducing cytotoxic stress and promoting cancer cell death. This dual-targeting mechanism represents a next-generation ADC strategy intended to enhance efficacy beyond traditional single-target approaches.
The therapy has received Breakthrough Therapy Designation (BTD) from the Center for Drug Evaluation under China’s National Medical Products Administration for multiple indications, and the U.S. Food and Drug Administration has granted BTD for previously treated non-small cell lung cancer patients with EGFR mutations. Additionally, New Drug Applications for two separate oncology indications have been accepted and included in China’s priority review process, signaling regulatory momentum behind the program.
Global Development and Regulatory Momentum
The BL-B01D1-307 study is sponsored by Sichuan Biokin Pharmaceutical Co., Ltd., SystImmune’s parent company, in Mainland China. Outside China, iza-bren is jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement. The companies indicated that detailed Phase III data will be presented at an upcoming medical meeting, which is expected to provide further insights into efficacy, safety, and subgroup analyses.
For Bristol Myers Squibb, the positive interim results reinforce its expanding oncology portfolio and strategic focus on advanced biologics and ADC technologies. For SystImmune, the data validate its platform approach centered on bispecific and multispecific antibody innovation. The achievement of dual PFS and OS endpoints at interim analysis strengthens the potential regulatory path forward and may position iza-bren as a meaningful new treatment option for patients with difficult-to-treat TNBC.
Triple-negative breast cancer remains one of the most aggressive subtypes of breast cancer, lacking expression of estrogen receptor, progesterone receptor, and HER2, thereby limiting targeted treatment options. The successful Phase III interim analysis of iza-bren marks a pivotal advancement in expanding precision oncology strategies for this high-risk patient population.
Source: Bristol Myers Squibb press release
