Iza-Bren Significantly Improves Overall and Progression-Free Survival in Triple-Negative Breast Cancer and Esophageal Cancer
SystImmune, Inc., a clinical-stage biotechnology company focused on developing innovative cancer therapies, and Bristol Myers Squibb have announced encouraging results from two pivotal Phase 3 clinical trials evaluating izalontamab brengitecan (iza-bren), an investigational EGFRxHER3 bispecific antibody-drug conjugate (ADC). The findings, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated statistically significant and clinically meaningful improvements in both overall survival (OS) and progression-free survival (PFS) in patients with advanced triple-negative breast cancer (TNBC) and recurrent or metastatic esophageal squamous cell carcinoma (ESCC).
The results were reported by Sichuan Biokin Pharmaceutical Co., Ltd. (Biokin), the parent company of SystImmune, and further strengthen the growing body of evidence supporting iza-bren as a potentially first-in-class bispecific ADC capable of addressing multiple difficult-to-treat cancers. The positive outcomes from these studies represent the third successful Phase 3 program for the therapy, following previously reported favorable results in recurrent or metastatic nasopharyngeal carcinoma (NPC) that were presented at the European Society for Medical Oncology (ESMO) Congress in 2025.
With positive Phase 3 outcomes now demonstrated across three distinct tumor types, researchers and clinicians increasingly view iza-bren as one of the most promising next-generation antibody-drug conjugates in oncology development.
Expanding the Potential of Bispecific Antibody-Drug Conjugates
Iza-bren is designed as a novel EGFRxHER3 bispecific antibody-drug conjugate, combining targeted antibody technology with a potent cytotoxic payload. By simultaneously targeting both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), the therapy seeks to improve tumor targeting while overcoming mechanisms that often contribute to treatment resistance.
This dual-targeting approach differentiates iza-bren from conventional ADCs and may provide broader activity across multiple cancer types characterized by EGFR and HER3 expression.
The latest Phase 3 findings are particularly significant because they establish important milestones in the development of bispecific ADCs. The PANKU-Breast02 study became the first Phase 3 trial of a bispecific ADC to demonstrate positive results for both progression-free survival and overall survival in patients with triple-negative breast cancer. Similarly, the PANKU-Esophagus01 trial became the first Phase 3 study of a bispecific ADC in esophageal cancer to achieve positive outcomes for both primary endpoints.
Dr. Yi Zhu, Chief Executive Officer of Biokin, highlighted the importance of these achievements.
According to Zhu, iza-bren has now demonstrated meaningful clinical benefit in three separate Phase 3 studies across different cancer indications, underscoring the potential value of its unique dual-targeting mechanism. He emphasized that the company remains committed to exploring the full therapeutic potential of the drug in an effort to improve outcomes for patients facing serious and often treatment-resistant cancers.
Cristian Massacesi, Executive Vice President, Chief Medical Officer and Head of Development at Bristol Myers Squibb, noted that the therapy may address a major unmet need among patients whose disease progresses following prior treatments. He also suggested that the drug could potentially move into earlier treatment settings and become a foundational therapy that can be combined with other cancer treatments.
Positive Phase 3 Results in Triple-Negative Breast Cancer
One of the most notable findings came from the Phase 3 PANKU-Breast02 trial, which evaluated iza-bren in patients with unresectable locally advanced or metastatic triple-negative breast cancer whose disease had progressed after one or two prior lines of systemic therapy.
Triple-negative breast cancer is widely regarded as one of the most aggressive forms of breast cancer. Unlike other breast cancer subtypes, TNBC lacks expression of estrogen receptors, progesterone receptors, and HER2, limiting the availability of targeted treatment options. Patients with advanced disease frequently experience rapid progression and poor long-term outcomes.
The study enrolled 418 patients who were randomly assigned to receive either iza-bren or physician’s choice chemotherapy. Standard chemotherapy options included eribulin, capecitabine, gemcitabine, and vinorelbine.
At a prespecified interim analysis, the study successfully met both primary endpoints.
After a median follow-up period of 11 months, patients treated with iza-bren achieved a median overall survival of 15.9 months compared with 12.5 months among patients receiving standard chemotherapy. This represented a 40% reduction in the risk of death.
The progression-free survival results were even more striking. Patients receiving iza-bren experienced a median progression-free survival of 8.5 months, compared with just 3.1 months in the chemotherapy arm. This translated into a 71% reduction in the risk of disease progression or death.
Additionally, objective response rates were substantially improved. More than half of patients receiving iza-bren achieved a confirmed tumor response, with an objective response rate of 51.7%, compared with 20.5% among patients receiving physician-selected chemotherapy.
Dr. Jiong Wu of Fudan University Shanghai Cancer Center noted that despite advances in breast cancer treatment, metastatic triple-negative breast cancer remains a major clinical challenge. He stated that the findings suggest iza-bren could emerge as a new standard of care for this patient population, becoming the first bispecific ADC to demonstrate improvements in both progression-free and overall survival in a Phase 3 TNBC trial.
Safety Findings in Breast Cancer Patients
The safety profile observed in the breast cancer study was generally consistent with previous clinical experience involving iza-bren.
Most severe treatment-emergent adverse events were hematologic in nature and aligned with the known effects of antibody-drug conjugate therapies.
Importantly, investigators reported no unexpected safety signals during the trial.
Interstitial lung disease (ILD), a potential concern with certain targeted therapies, was observed at low rates. Any-grade ILD occurred in only three patients receiving iza-bren, representing approximately 1.4% of treated participants. No cases were reported in the chemotherapy group.
Treatment discontinuations due to adverse events remained uncommon, occurring in fewer than 2% of patients treated with iza-bren.
These findings suggest that the significant efficacy benefits observed in the study were achieved while maintaining a manageable safety profile.
Strong Survival Benefits in Esophageal Squamous Cell Carcinoma
The second major Phase 3 study, PANKU-Esophagus01, evaluated iza-bren in patients with recurrent or metastatic esophageal squamous cell carcinoma whose disease had progressed following first-line treatment with a PD-1 or PD-L1 inhibitor combined with platinum-based chemotherapy.
Esophageal squamous cell carcinoma is among the most aggressive gastrointestinal cancers and remains associated with poor long-term survival. Once patients experience disease progression following frontline therapy, treatment options become limited and outcomes are generally unfavorable.
The trial enrolled nearly 500 patients and compared iza-bren with physician-selected chemotherapy.
Results from the interim analysis demonstrated significant improvements across all major efficacy measures.
Patients treated with iza-bren achieved a median overall survival of 9.8 months compared with 7.2 months among those receiving chemotherapy. This represented a 36% reduction in the risk of death.
Median progression-free survival improved from 2.0 months with chemotherapy to 4.2 months with iza-bren, corresponding to a 50% reduction in disease progression risk.
The therapy also generated substantially higher response rates. Investigators reported an objective response rate of 35.3% for iza-bren, compared with 13.1% for chemotherapy.
Dr. Lin Shen of Peking University Cancer Hospital and Institute emphasized the significance of these findings, noting that metastatic esophageal squamous cell carcinoma remains associated with a five-year survival rate below 5%. He stated that the study represents the first Phase 3 trial of an EGFRxHER3 bispecific ADC to deliver positive results in this patient population and could establish a new treatment benchmark for extending survival.
Safety Profile in Esophageal Cancer
The safety findings in the esophageal cancer trial were also considered manageable and generally consistent with expectations for a potent antibody-drug conjugate.
Grade 3 or higher treatment-related adverse events occurred more frequently in patients receiving iza-bren than in those receiving chemotherapy, largely driven by hematologic toxicities. However, discontinuation rates remained low, affecting only 2% of patients treated with iza-bren.
Treatment-related deaths were uncommon and occurred at similar rates between the treatment groups.
Investigators also reported low rates of interstitial lung disease, with severe cases remaining rare.
Overall, researchers concluded that the safety profile was acceptable in light of the substantial improvements observed in survival and disease control.
Regulatory Progress and Future Development
The positive clinical data are already supporting regulatory advancement. A New Drug Application seeking approval of iza-bren for recurrent or metastatic esophageal squamous cell carcinoma has been accepted by the Center for Drug Evaluation under China’s National Medical Products Administration. The application has also been granted priority review status, potentially accelerating the regulatory evaluation process.
The PANKU-Breast02 and PANKU-Esophagus01 trials were sponsored by Biokin in mainland China. Outside China, development of iza-bren is being conducted through a strategic collaboration between SystImmune and Bristol Myers Squibb.
With three successful Phase 3 studies now completed across triple-negative breast cancer, esophageal squamous cell carcinoma, and nasopharyngeal carcinoma, iza-bren is rapidly emerging as one of the most promising investigational ADCs in oncology. The breadth of positive clinical data suggests the therapy may have applications across multiple tumor types and could eventually become an important component of future cancer treatment strategies worldwide.
About iza-bren
Iza-bren (BL-B01D1) is a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3, which are highly expressed in various epithelial cancers and are known to be associated with cancer cell proliferation and survival. Iza-bren’s dual mechanism of action blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. In addition, upon antibody mediated internalization, iza-bren’s therapeutic novel Topo1i payload is released causing cytotoxic stress that leads to cancer cell death.
About SystImmune
SystImmune is a clinical-stage biopharmaceutical company located in Redmond, WA. It specializes in developing innovative cancer treatments using its established drug development platforms, focusing on bi-specific, multi-specific antibodies, and antibody-drug conjugates (ADCs). SystImmune has several assets in various stages of clinical trials for solid tumor and hematologic indications. Alongside ongoing clinical trials, SystImmune has a robust preclinical pipeline of potential cancer therapeutics in the discovery or IND-enabling stages, representing cutting-edge biologics development.
About Bristol Myers Squibb: Transforming Patients’ Lives Through Science
At Bristol Myers Squibb, our mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. We are pursuing bold science to define what’s possible for the future of medicine and the patients we serve.
