Iza-bren Yields Statistically Significant Efficacy in Advanced TNBC

Statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) were noted with izalontamab brengitecan (iza-bren) for patients with unresectable locally advanced or metastatic triple-negative breast cancer with disease progression after prior taxane therapy, according to a press release from Bristol Myers Squibb.¹

Iza-bren was assessed in in the phase 3 BL-B01D1-307 trial (NCT06382142), with these results being reported at the interim analysis. Iza-bren was designed as an EGFRxHER3 bispecific antibody drug conjugate (ADC). The full data will be presented at an upcoming meeting.

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

This is the third phase 3 trial in which iza-bren has achieved the primary end points. Additionally, it is the first bispecific ADC to have positive PFS and OS for patients with triple-negative breast cancer.

While the primary end points were PFS and OS, the secondary end points included objective response rate, disease control rate, duration of response, treatment-emergent adverse effects, and the frequency of anti-drug antibody.²

Iza-bren is to be administered intravenously (IV) for a cycle of 3 weeks plus either eribulin as an IV bolus, vinorelbine as IV infusion, gemcitabine as IV infusion, or oral capecitabine for a total cycle of 3 weeks. If patients experienced a clinical benefit, they could receive additional treatment. Treatment would be stopped if disease progression or intolerable toxicity occurred.

To date, 418 patients have been enrolled, with a primary completion and collection date of June 2026. Currently, the trial is open in China for patients 18 to 75 years old.

Patients were included in the trial if they had an expected survival of 3 months or longer, provided archival tumor tissue samples or fresh tissue samples of primary metastatic lesions within 3 years, and had received 1 to 2 lines of prior chemotherapy in the locally advanced or metastatic stage or had metastatic lesions within 3 years. If baseline brain metastases were present, they should have been stable, and patients must have received treatment for them. Additionally, patients needed to have no severe cardiac dysfunction, no blood transfusion or use of cell growth factors/platelet raising drugs within 14 days before administration of study drug, and a urine protein of 2 or less plus less than 1000 mg per 24 hours.

Patients were excluded from treatment if they had a prior ADC with a TOPI inhibitor as a toxin; prior receipt of an ADC or antibody drug targeting EGFR and/or HER3; specific previous therapy within a constrained time frame including chemotherapy, immunotherapy, or radiotherapy; an anthracycline cumulative equivalent dose of doxorubicin (Adriamycin) of more than 360 mg/m²; a history of severe cardiovascular or cerebrovascular disease; unstable thrombotic events that required therapeutic intervention within 6 months of screening; QT prolongation; and active malignancy diagnosed within 5 years before randomization.

“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.¹ “We look forward to advancing the science and development of ADCs, with the hope of uncovering new options for people living with cancer.”

Breakthrough therapy designation (BTD) has been granted to iza-bren by China’s National Medical Products Administration for 7 indications, and the FDA has granted breakthrough therapy designation for previously treated non–small cell lung cancer with an EGFR mutation.³

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. Accessed February 26, 2026. https://tinyurl.com/6dtzawca
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://tinyurl.com/4nrstnkf
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://tinyurl.com/57v98uxb