Iza-Bren Improves Survival in Phase 3 Triple-Negative Breast Cancer Study

Sichuan Biokin Pharmaceutical Co., Ltd. (Biokin), SystImmune Inc. and Bristol Myers Squibb have announced that the bispecific antibody-drug conjugate izalontamab brengitecan (iza-bren) achieved positive topline results, improving survival and delaying progression in a phase 3 study for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose disease progressed after prior taxane therapy.

Main data that support the findings

In a pre-specified interim analysis of the clinical trial, iza-bren demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of progression-free survival (PFS) and overall survival (OS). PFS refers to the length of time during and after treatment that a patient lives with the disease without it getting worse, while OS measures the length of time patients remain alive.

These results were compared against chemotherapy of physician’s choice. According to the announcement, this marks the first time a bispecific antibody-drug conjugate (ADC) in a phase 3 study has reported dual positive PFS and OS results specifically for the treatment of triple-negative breast cancer. This study also represents the third phase 3 trial in which iza-bren has successfully achieved its primary endpoints.

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

Cristian Massacesi, executive vice president, chief medical officer and head of development at Bristol Myers Squibb, noted in the news release that the results underscore the potential of this technology to change outcomes in cancers that are considered difficult to treat. The companies intend to present the full data from this analysis at an upcoming medical meeting.

Trial details

The BL-B01D1-307 study is a Phase 3, randomized, open-label, multi-center clinical trial conducted in Mainland China. It focuses on patients with triple-negative breast cancer that is either unresectable locally advanced or metastatic. To be eligible for the study, patients must have seen their disease progress following prior treatment with taxane therapy.

Iza-bren is a bispecific ADC designed to target two different proteins: EGFR and HER3. These proteins are often highly expressed in various epithelial cancers and are known to contribute to the growth and survival of cancer cells. The drug employs a dual mechanism of action. First, it blocks signals from EGFR and HER3 to the cancer cells, which reduces the signals that tell the cells to grow. Second, once the antibody is internalized by the cell, it releases a therapeutic novel Topo1i payload. This payload causes cytotoxic stress, which leads to the death of the cancer cell.

Outside of China, iza-bren is being jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement. The drug has received several regulatory recognitions, including breakthrough therapy designation (BTD) from the Center for Drug Evaluation (CDE) in China for seven different indications. In the United States, the FDA has granted BTD to iza-bren for the treatment of patients with previously treated non-small cell lung cancer (NSCLC) who have an EGFR mutation.

Additionally, the CDE has accepted new drug applications (NDAs) for iza-bren for the treatment of locally advanced or metastatic nasopharyngeal carcinoma and recurrent or metastatic esophageal squamous cell carcinoma. These applications have been included in the priority review process.

Safety

While specific adverse event rates were not detailed in the topline summary of the BL-B01D1-307 interim analysis, the safety profile of iza-bren is being monitored as part of its ongoing clinical development. The phase 3 trial is designed to evaluate the efficacy and safety of the ADC in comparison to standard chemotherapy of physician's choice.

The mechanism of the drug involves a targeted delivery of its payload to cells expressing EGFR and HER3, intended to induce cancer cell death through cytotoxic stress. As a clinical-stage treatment, iza-bren continues to undergo evaluation across multiple cancer types, including solid tumors and hematologic indications, to further define its safety and therapeutic role for patients with cancer.

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; https://news.bms.com/news/corporate-financial/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

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.