Biokin’s Iza-Bren Hits Phase 3 PFS Endpoint in HR+/HER2− Breast Cancer, Marking 5th Phase 3 Success
Biokin Pharmaceutical’s first-in-class EGFR×HER3 bispecific antibody-drug conjugate izalontamab brengitecan (iza-bren; BL-B01D1) has delivered another positive Phase 3 readout, meeting the progression-free survival endpoint in previously treated HR-positive/HER2-negative advanced breast cancer. The result marks the fifth Phase 3 study of iza-bren to reach its primary endpoint and further broadens the late-stage evidence supporting the bispecific ADC.
Sichuan Biokin Pharmaceutical announced that its Phase 3 BL-B01D1-306 (PANKU-Breast01) study has met its primary endpoint of progression-free survival (PFS) at a prespecified interim analysis.
According to the company disclosure reported August 26, an independent Data Monitoring Committee (iDMC) determined that iza-bren met the PFS primary endpoint in patients with unresectable locally advanced, recurrent or metastatic hormone receptor-positive, HER2-negative (HR+/HER2−) breast cancer who had failed at least one previous line of chemotherapy. (CFi)
The achievement represents the fifth Phase 3 trial of iza-bren to meet its primary endpoint, according to Biokin. The company also described BL-B01D1-306 as the first Phase 3 trial of a bispecific ADC to reach its primary endpoint in HR+/HER2− breast cancer. (CFi)
Iza-Bren Versus Physician’s Choice Chemotherapy
BL-B01D1-306 (NCT06343948) is a randomized, open-label, multicenter Phase 3 trial evaluating iza-bren against chemotherapy of the investigator’s choice.
The study enrolled patients with unresectable locally advanced, recurrent or metastatic HR+/HER2− breast cancer following failure of at least one prior chemotherapy regimen. The control options include eribulin, capecitabine, gemcitabine or vinorelbine. (ClinicalTrials.gov)
The trial began in April 2024 and is registered under both NCT06343948 and BL-B01D1-306. (ClinicalTrials.gov)
Biokin has not yet disclosed the numerical PFS results—including median PFS, hazard ratio or confidence intervals—or detailed safety findings from the interim analysis. Those data will ultimately determine the magnitude and clinical significance of iza-bren’s advantage over chemotherapy.
Nevertheless, crossing the prespecified efficacy threshold at an interim analysis represents another important late-stage validation for the program.
Expanding Iza-Bren Into the Largest Breast Cancer Subtype
The result is particularly notable because HR+/HER2− disease represents the most common molecular subtype of breast cancer.
Treatment of advanced HR+/HER2− breast cancer has evolved substantially with endocrine therapy, CDK4/6 inhibitors and newer targeted therapies. However, patients whose tumors progress through endocrine and targeted treatment eventually may require chemotherapy, and additional effective therapies remain needed in later-line disease.
BL-B01D1-306 is targeting precisely this setting: patients with advanced disease who have already failed at least one chemotherapy regimen.
A positive Phase 3 trial therefore opens another potentially large indication for iza-bren beyond the tumor types in which the drug has already demonstrated late-stage activity.
A Different Approach to ADC Targeting
Iza-bren is designed as an EGFR×HER3 bispecific ADC, simultaneously recognizing two members of the ErbB receptor family.
Rather than relying on a single tumor-associated antigen, the bispecific architecture is intended to exploit expression of both EGFR and HER3 and potentially increase tumor targeting across heterogeneous cancer-cell populations.
The ADC carries a topoisomerase inhibitor payload. A registered clinical study describes iza-bren as a bispecific ADC directed against EGFR and HER3 with a topoisomerase inhibitor payload. (ClinicalTrials.gov)
That design has allowed Biokin and its U.S. subsidiary SystImmune to investigate the drug across numerous solid tumors rather than limiting development to a single biomarker-defined cancer.
Biokin says more than 40 clinical studies of iza-bren are underway in China and the United States, including 20 Phase 3 or Phase 2/3 studies. Seven indications have received Breakthrough Therapy designation from China’s Center for Drug Evaluation, while one has received Breakthrough Therapy designation from the U.S. FDA. (CFi)
Fifth Phase 3 Trial to Reach Its Primary Endpoint
The consistency of iza-bren’s Phase 3 program is becoming one of the most notable aspects of the asset.
BL-B01D1-306 is now the fifth Phase 3 study in which iza-bren has reached its primary endpoint, according to Biokin’s latest disclosure. (CFi)
Earlier this year, iza-bren also produced positive Phase 3 results in triple-negative breast cancer (TNBC).
In February, SystImmune and Bristol Myers Squibb announced that the Phase 3 BL-B01D1-307 study met both PFS and overall survival (OS) primary endpoints in previously treated unresectable locally advanced or metastatic TNBC.
In that study, iza-bren demonstrated statistically significant and clinically meaningful improvements in both PFS and OS compared with physician’s choice chemotherapy. At the time, BL-B01D1-307 represented the third Phase 3 iza-bren trial to achieve its primary endpoint or endpoints. (Bristol Myers Squibb)
Iza-bren has also generated pivotal results in other tumor types, including nasopharyngeal carcinoma, esophageal squamous cell carcinoma and EGFR-mutated non-small cell lung cancer (NSCLC).
Already Approved in Two Cancer Indications in China
Iza-bren is no longer simply an experimental ADC.
The drug has already received Chinese regulatory approval for two indications: recurrent or metastatic nasopharyngeal carcinoma and recurrent or metastatic esophageal squamous cell carcinoma. Biokin also says its marketing application in locally advanced or metastatic triple-negative breast cancer has been accepted by China’s Center for Drug Evaluation. (CFi)
The esophageal cancer approval was supported by the Phase 3 PANKU-Esophagus01/BL-B01D1-305 trial, which demonstrated statistically significant and clinically meaningful improvements in both PFS and OS versus chemotherapy. (PR Newswire)
The growing number of successful trials raises the possibility that iza-bren could evolve into a broadly used ADC franchise spanning several major solid tumors.
Bristol Myers Squibb Partnership Adds Global Importance
The clinical progress also has major implications beyond Biokin.
Iza-bren is being jointly developed outside China by Biokin subsidiary SystImmune and Bristol Myers Squibb (BMS) under their global strategic partnership. Bristol Myers Squibb and SystImmune entered their collaboration around BL-B01D1 in late 2023, giving BMS an important position in the global development of the asset.
The partnership put one of China’s most advanced bispecific ADC programs into the pipeline of a major global pharmaceutical company and became an early example of the surge in China-originated oncology licensing transactions.
The expanding Phase 3 dataset strengthens the strategic importance of that collaboration.
Key Numbers Still Needed
The topline result is clearly positive, but the most important clinical details have yet to be disclosed.
Biokin has not announced the PFS hazard ratio, median PFS in either arm, objective response rate, duration of response, overall survival results or detailed adverse-event profile from BL-B01D1-306.
Those data will be especially important in HR+/HER2− breast cancer, where the treatment landscape is increasingly competitive and includes multiple ADCs and targeted therapies.
The durability of benefit and toxicity profile will therefore matter alongside the headline PFS result when assessing iza-bren’s potential position in the treatment sequence.
Iza-Bren’s Phase 3 Momentum Continues
Even with those questions outstanding, BL-B01D1-306 adds another important piece to an increasingly substantial body of Phase 3 evidence.
Iza-bren has progressed from an unusual Chinese bispecific ADC program into a commercial-stage oncology drug with two Chinese approvals, a major global partnership with BMS and a rapidly expanding portfolio of successful registrational trials.
The HR+/HER2− result is particularly important because it demonstrates Phase 3 efficacy in another major breast cancer population following the drug’s positive results in triple-negative disease.
And with five Phase 3 studies now having reached their primary endpoints, iza-bren is building an unusually broad late-stage clinical record for a next-generation ADC.
The next major question is no longer simply whether BL-B01D1-306 is positive. It is how large the PFS benefit is—and whether the full efficacy and safety dataset is strong enough to make iza-bren a competitive new treatment option in advanced HR+/HER2− breast cancer.
References
- Sichuan Biokin Pharmaceutical. “Voluntary Disclosure Regarding Interim Analysis of the Phase III Clinical Trial of Iza-bren (BL-B01D1) in Locally Advanced, Recurrent or Metastatic HR+/HER2− Breast Cancer.” August 26, 2026.
https://cfi.net.cn/p20260826001317.html - ClinicalTrials.gov. “A Study Comparing BL-B01D1 With Chemotherapy of Physician’s Choice in Patients With Unresectable Locally Advanced, Recurrent, or Metastatic HR+/HER2− Breast Cancer (PANKU-Breast01).” NCT06343948 / BL-B01D1-306.
https://clinicaltrials.gov/study/NCT06343948 - SystImmune and Bristol Myers Squibb. “Positive Phase III Interim Topline Results for Izalontamab Brengitecan (Iza-bren) in Previously Treated Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer.” 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 - SystImmune. “Second Approval of Iza-bren in China for the Treatment of Recurrent or Metastatic Esophageal Squamous Cell Carcinoma.” July 17, 2026.
https://www.prnewswire.com/news-releases/systimmune-announces-second-approval-of-iza-bren-in-china-for-the-treatment-of-recurrent-or-metastatic-esophageal-squamous-cell-carcinoma-302827983.html
