Izalontamab Brengitecan Demonstrates Significant PFS, OS Benefit in Phase III Trial for Pretreated Triple-Negative Breast Cancer

Topline results from a pre-specified interim analysis of the Phase III BL-B01D1-307 trial (NCT06382142) show that izalontamab brengitecan (iza-bren) achieved statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) compared with physician’s choice of chemotherapy in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose disease progressed after prior taxane therapy.^1,2

The potential first-in-class therapy is being developed by Biokin in China and jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement outside of China.

The study achieved the dual primary endpoints of PFS and OS at the time of the interim analysis. These results mark the third Phase III trial in which iza-bren achieved the primary endpoint or endpoints. Further, it’s the first Phase III trial of a bispecific antibody-drug conjugate (ADC) in TNBC to report dual positive PFS and OS results, according to the study investigators.

“Patients with advanced triple-negative breast cancer who progress after standard therapies face an urgent need for more effective options,” said Yi Zhu, Biokin CEO, in a press release. “These topline results further strengthen our confidence in iza-bren’s potential to deliver meaningful clinical benefit across multiple cancers.”¹

Full data from the interim analysis are expected to be presented at an upcoming medical meeting.

Trial Design

• The randomized, open-label, multicenter BL-B01D1-307 trial is being conducted in China and evaluates iza-bren in patients with unresectable locally advanced or metastatic TNBC whose disease progressed following prior taxane therapy.
• Patients were randomly assigned to receive iza-bren or chemotherapy of physician’s choice.
• The dual primary endpoints are progression-free survival and overall survival.

Regulatory Status and Development Program

Iza-bren is a bispecific ADC that acts by targeting both epidermal growth factor receptor and human epidermal growth factor receptor 3 (EGFRxHER3) with a topoisomerase 1 inhibitor payload.

Iza-bren was designed to target both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), which are frequently overexpressed in epithelial malignancies and are associated with tumor growth and survival signaling pathways. The agent combines dual receptor targeting with a topoisomerase I inhibitor payload intended to induce cytotoxic stress following internalization into tumor cells.

The Center for Drug Evaluation under China’s National Medical Products Administration has granted Breakthrough Therapy Designation to iza-bren for seven indications. The FDA granted the drug with Breakthrough Therapy Designation in August 2025 for previously treated non–small cell lung cancer patients with an EGFR mutation.³

In China, new drug applications for locally advanced or metastatic nasopharyngeal carcinoma and for recurrent or metastatic esophageal squamous cell carcinoma have been accepted and placed under priority review.

Three Key Takeaways from the BL-B01D1-307 trial

• The interim analysis met dual primary endpoints of progression-free and overall survival, strengthening the evidentiary bar for bispecific ADCs in late-line TNBC.
• BL-B01D1-307 is among the first Phase III trials in TNBC to demonstrate dual PFS and OS benefit with a bispecific ADC mechanism targeting EGFR and HER3.
• Ongoing global development and multiple Breakthrough Therapy Designations suggest regulatory momentum and potential expansion into additional tumor types.

“These results underscore the potential of bispecific ADC technology targeting both EGFR and HER3 to meaningfully change outcomes in difficult-to-treat cancers,” said Cristian Massacesi, executive vice president, chief medical officer and head of Development at Bristol Myers Squibb. “We look forward to advancing the science and development of ADCs, with the hope of uncovering new options for people living with cancer.”¹

References

1. SystImmune and Bristol Myers Squibb Highlight Positive Phase III Interim Topline Results for izalontamab brengitecan (Iza-bren) in Previously Treated Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer. News release. Bristol Myers Squibb. February 26, 2026. https://news.bms.com/news/details/2026/SystImmune-and-Bristol-Myers-Squibb-Highlight-Positive-Phase-III-Interim-Topline-Results-for-izalontamab-brengitecan-Iza-bren-in-Previously-Treated-Unresectable-Locally-Advanced-or-Metastatic-Triple-Negative-Breast-Cancer/default.aspx

2. A Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer. ClinicalTrials.gov. Updated November 17, 2025. Accessed February 26, 2026. https://clinicaltrials.gov/study/NCT06382142

3. Izalontamab Brengitecan (EGFRxHER3 ADC) Granted Breakthrough Therapy Designation by U.S. FDA for Patients with Previously Treated Advanced EGFR-Mutated Non-Small Cell Lung Cancer. News release. Bristol Myers Squibb. August 18, 2025. Accessed February 26, 2026. https://news.bms.com/news/corporate-financial/2025/Izalontamab-Brengitecan-EGFRxHER3-ADC-Granted-Breakthrough-Therapy-Designation-by-U-S--FDA-for-Patients-with-Previously-Treated-Advanced-EGFR-Mutated-Non-Small-Cell-Lung-Cancer/default.aspx