Iza-Bren Meets PFS and OS End Points in Phase 3 TNBC Trial

In a significant development for the management of aggressive breast cancer subtypes, an interim analysis demonstrated that the bispecific antibody-drug conjugate (ADC) izalontamab brengitecan (iza-bren; BL-B01D1) achieved statistically significant and clinically meaningful improvements in its dual primary end points of progression-free survival (PFS) and overall survival (OS) compared with chemotherapy of physician’s choice in patients with previously treated metastatic triple-negative breast cancer (TNBC).¹

The full data will be presented at an upcoming medical meeting.

The BL-B01D1-307 study (NCT06382142) focused on a challenging patient population: those with unresectable locally advanced or metastatic TNBC whose disease had progressed following prior taxane-based chemotherapy. The lack of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression to target in these tumors contributes to their difficult-to-treat nature.²

First Bispecific ADC to Show Dual Survival Benefit

Iza-bren is a first-in-class bispecific ADC designed to simultaneously target EGFR and HER3. The receptors are present in about 50% and 30% of TNBC cases, respectively.³ Iza-bren utilizes a topoisomerase I inhibitor payload, which is released upon antibody-mediated internalization, inducing genotoxic stress and subsequent apoptosis in cancer cells.¹

This marks the first time a bispecific ADC has demonstrated a dual benefit in both PFS and OS within a phase 3 trial for TNBC. While standard chemotherapy options offer limited durability in the second-line and later settings, the interim results for iza-bren suggest a potential shift in the treatment paradigm.

“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, in a news release. “We look forward to advancing the science and development of ADCs, with the hope of uncovering new options for people living with cancer.”

Broad Clinical Development and Regulatory Status

Beyond breast cancer, iza-bren is being evaluated across several solid tumors. The FDA previously granted breakthrough therapy designation (BTD) to the agent for the treatment of patients with previously treated EGFR-mutated non–small cell lung cancer.⁴

The Center for Drug Evaluation (CDE) under China’s National Medical Products Administration granted BTD to iza-bren for the treatment of 7 indications.¹ The new drug applications for 2 indications of iza-bren, for the treatment of locally advanced or metastatic nasopharyngeal carcinoma and for the treatment of recurrent or metastatic esophageal squamous cell carcinoma, have been accepted by the CDE and included in the priority review process.

Additionally, data presented at the 2025 ESMO Congress showed that iza-bren led to improved response rates vs chemotherapy in nasopharygeal cancer.⁵

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. February 26, 2026. Accessed February 26, 2026. https://tinyurl.com/4y5cxjvb

2. Obidiro O, Battogtokh G, Akala EO. Triple negative breast cancer treatment options and limitations: Future outlook. Pharmaceutics. 2023 Jun 23;15(7):1796. doi: 10.3390/pharmaceutics15071796. PMID: 37513983; PMCID: PMC10384267.

3. Ogden A, Bhattarai S, Sahoo B, et al. Combined HER3-EGFR score in triple-negative breast cancer provides prognostic and predictive significance superior to individual biomarkers. Sci Rep. 2020 Feb 20;10(1):3009. doi: 10.1038/s41598-020-59514-1. PMID: 32080212; PMCID: PMC7033213.

4. 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. SystImmune Inc. August 18, 2025. Accessed February 26, 2026. https://tinyurl.com/58pzbsz2

5. Yang Y, Zhou H, Tang L, et al. Iza-bren (BL-B01D1), an EGFR×HER3 bispecific antibody-drug conjugate, versus physician's choice of chemotherapy in heavily pretreated recurrent/metastatic nasopharyngeal carcinoma: a randomized, open-label, multicenter, phase III, pivotal study (BL-B01D1-303). Presented at: 2025 European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA35.