Author(s)Ashling Wahner
Fact checked by: Chris Ryan
- An EGFR- and HER3-directed bispecific ADC demonstrated superiority over eribulin, vinorelbine, gemcitabine, or capecitabine in previously treated advanced TNBC, improving both PFS and OS.
- BL-B01D1-307 enrolled adults 18–75 years with ECOG 0–1, RECIST 1.1 measurable disease, and 1–2 prior metastatic chemotherapy lines including a taxane.
- Treatment consisted of IV iza-bren on 3‑week cycles continued with clinical benefit until progression/toxicity; chemotherapy control followed the same cadence.
- Secondary endpoints included ORR, DCR, DoR, TEAEs, and anti–iza-bren antibody incidence, supporting a comprehensive efficacy, safety, and immunogenicity assessment.
- Regulatory activity spans FDA breakthrough therapy designation for advanced EGFR-mutant NSCLC and multiple China CDE breakthrough designations with NDAs under review in ESCC and NPC.
Izalontamab brengitecan (iza-bren; BL-B01D1)generated statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) outcomes compared with chemotherapy of physician’s choice in patients with previously treated, unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) who experienced disease progression following prior taxane therapy, meeting the dual primary end points of the phase 3 BL-B01D1-307 trial (NCT06382142).1
Data from this prespecified interim analysis of the trial are planned to be presented at a future medical meeting.
“Patients with advanced TNBC who progress after standard therapies face an urgent need for more effective options,” Yi Zhu, PhD, chief executive officer of Biokin, stated in a news release. “These topline results further strengthen our confidence in iza-bren’s potential to deliver meaningful clinical benefit across multiple cancers.”
What is the mechanism of action of iza-bren and the regulatory history of this agent in oncology?
Iza-bren is an EGFR- and HER3-directed bispecific antibody-drug conjugate (ADC). The BL-B01D1-307 trial is the third phase 3 study in which iza-bren has reached the primary end points and the first phase 3 study to read out with both PFS and OS results favoring the ADC in patients with TNBC.
In August 2025, the FDA granted breakthrough therapy designation to iza-bren for the treatment of patients with locally advanced or metastatic non–small cell lung cancer harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations who have disease progression during or following treatment with an EGFR-directed TKI and platinum-based chemotherapy.2
The agent has also received breakthrough therapy designation in China from the Center for Drug Evaluation (CDE) under the National Medical Products Administration across 7 indications.1 Additionally, the CDE has accepted for review 2 new drug applications for the agent, one for the treatment of patients with recurrent or metastatic esophageal squamous cell carcinoma, and one for the treatment of patients with locally advanced or metastatic nasopharyngeal carcinoma.
What is the design of the BL-B01D1-307 trial?
This randomized, open-label, multicenter trial enrolled patients between 18 and 75 years of age with unresectable, locally advanced or metastatic TNBC.3 Patients needed to have received 1 or 2 prior lines of chemotherapy in the locally advanced or metastatic settings, as well as a prior taxane. Patients also needed to have an expected survival time of at least 3 months, at least 1 measurable disease per RECIST 1.1 criteria, and an ECOG performance score of 0 or 1.
Patients in the investigational arm received iza-bren as an intravenous infusion for 1 3-week cycle. Those with clinical benefit could continue to receive iza-bren for additional cycles. Iza-bren treatment continued until disease progression, intolerable toxicity, or other reasons. Patients in the control arm received physician’s choice of eribulin, vinorelbine, gemcitabine, or capecitabine on the same treatment cadence as in the investigational arm.
PFS and OS serve as the co-primary end points. Secondary end points include overall response rate, disease control rate, duration of response, treatment-emergent adverse effects, and the frequency of anti–iza-bren antibodies.
“These results underscore the potential of bispecific ADC technology targeting both EGFR and HER3 to meaningfully change outcomes in difficult‑to‑treat cancers,” Cristian Massacesi, executive vice president, chief medical officer, and head of Development at Bristol Myers Squibb, added in the news release.1 “We look forward to advancing the science and development of ADCs, with the hope of uncovering new options for people living with cancer.”
References
- 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://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
- 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 August 18, 2025. https://news.bms.com/news/details/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
- 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 7, 2025. Accessed February 26, 2026. https://clinicaltrials.gov/study/NCT06382142