On June 2, 2026 SystImmune, Inc. (SystImmune), a clinical-stage biotechnology company, and Bristol Myers Squibb (NYSE: BMY) reported that SystImmune’s parent company, Sichuan Biokin Pharmaceutical Co., Ltd. (Biokin), reported positive results from prespecified interim analyses of two Phase 3 studies evaluating izalontamab brengitecan (iza-bren), an investigational and potentially first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC). The studies demonstrated iza-bren achieved statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) in heavily pretreated, unresectable locally advanced or metastatic triple-negative breast cancer (TNBC; PANKU-Breast02/BL-B01D1-307) and recurrent or metastatic esophageal squamous cell carcinoma (ESCC; PANKU-Esophagus01/BL-B01D1-305). These data, presented at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, support iza-bren’s potential as a new standard of care in these challenging cancer types.
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Iza-bren has now shown clinical benefit in three Phase 3 trials, underscoring its broad therapeutic potential. PANKU-Breast02 is the first Phase 3 study of a bispecific ADC to report positive results for dual primary endpoints of both PFS and OS in TNBC, while PANKU-Esophagus01 marks the first Phase 3 trial of a bispecific ADC in esophageal cancer to report positive dual primary endpoints of both PFS and OS. Iza-bren previously demonstrated positive phase 3 results in recurrent or metastatic nasopharyngeal carcinoma (NPC), presented at ESMO (Free ESMO Whitepaper) 2025.
"As a potentially first-in-class EGFRxHER3 bispecific antibody-drug conjugate, iza-bren has now shown significant clinical benefit in three Phase 3 trials in different cancer types, and the strength of these data presented at ASCO (Free ASCO Whitepaper) further reinforce the value iza-bren can deliver over current standards of care," said Dr. Yi Zhu, chief executive officer of Biokin. "We are proud to share these results as we continue to evaluate iza-bren to unlock the full potential of this dual mechanism of action to improve outcomes for patients in need."
"Iza-bren can address a critical gap for patients who develop resistance or experience disease progression after prior therapies and may also hold potential in earlier lines of therapy," said Cristian Massacesi, MD, executive vice president, chief medical officer and head of development, Bristol Myers Squibb. "We have a broad development program for iza-bren and believe it has the potential to be a cornerstone treatment in a number of different cancers and easily combined with other therapies."
Results from the Interim Analysis of PANKU-Breast02 (BL-B01D1-307)
The Phase 3 PANKU-Breast02 trial evaluated iza-bren in patients with unresectable locally advanced or metastatic TNBC whose disease progressed following 1-2 prior lines of systemic therapy for advanced disease, including prior taxane therapy. Patients were randomized 1:1 to receive iza-bren (n=207) or physician’s choice of chemotherapy (TPC; n=211), which included eribulin, capecitabine, gemcitabine, or vinorelbine. The study met both dual primary endpoints at a prespecified interim analysis, demonstrating a statistically significant and clinically meaningful improvement in OS and BICR-assessed PFS with iza-bren compared to TPC.
With a median follow-up of 11 months, median OS was 15.9 months with iza-bren vs. 12.5 months with TPC (HR: 0.60; 95% CI: 0.42-0.85; p=0.0019)
Median PFS by Blinded Independent Central Review (BICR) was 8.5 months with iza-bren vs. 3.1 months with TPC (HR: 0.29; 95% CI: 0.22-0.38; p<0.0001)
The confirmed objective response rate (ORR) assessed by BICR was 51.7% with iza-bren compared to 20.5% with TPC (odds ratio, 4.3; 95% CI: 2.8-6.7)
"While there have been significant advancements in breast cancer treatment, advanced triple-negative breast cancer has remained a challenge, with patients facing poor outcomes," said Dr. Jiong Wu, Fudan University Shanghai Cancer Center. "These results highlight the potential for iza-bren to be a new standard of care as the first bispecific ADC to show improved progression-free and overall survival in a Phase 3 study in this patient population."
Iza-bren showed a manageable safety profile in this heavily pre-treated patient population, with no new safety signals observed. Grade >3 treatment-emergent adverse events (TEAEs) were predominantly hematologic toxicities and consistent with the known safety profile of iza-bren. Any grade interstitial lung disease (ILD) was reported in 3 (1.4%; 1 case of grade 1 and 2 cases of grade 2) patients treated with iza-bren and 0 patients treated with TPC. Treatment discontinuation due to TEAEs occurred in 4 (1.9%) patients treated with iza-bren and 1 (0.5%) patients treated with TPC.
Results from the Interim Analysis of PANKU-Esophagus01 (BL-B01D1-305)
The Phase 3 PANKU-Esophagus01 trial evaluated iza-bren in patients with recurrent or metastatic esophageal squamous cell carcinoma who had progressed after first-line treatment with a PD-1/PD-L1 inhibitor plus platinum-based chemotherapy (n=249) compared to chemotherapy of physician’s choice (n=248). Results from the interim analysis show iza-bren demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoints of OS and BICR-assessed PFS.
Median OS was 9.8 months with iza-bren vs. 7.2 months with chemotherapy (HR: 0.64; 95% CI: 0.49-0.83; p=0.0004).
Median PFS by BICR was 4.2 months with iza-bren vs. 2.0 months with chemotherapy (HR:0.50; 95% CI: 0.40-0.63; p<0.0001).
Iza-bren also demonstrated an improvement in responses with an ORR by BICR of 35.3% compared to 13.1% with chemotherapy.
"Metastatic esophageal squamous cell carcinoma is an aggressive disease with a five-year survival rate of less than 5%, and there remains a critical unmet need for treatment options after first-line immunotherapy and chemotherapy," said Dr. Lin Shen, Peking University Cancer Hospital and Institute. "As the first Phase 3 clinical trial of a novel EGFRxHER3 bispecific antibody-drug conjugate to report positive data in this patient population, these results show the potential for iza-bren to set a new benchmark in significantly extending survival for patients with recurrent or metastatic esophageal squamous cell carcinoma."
Iza-bren also showed a manageable safety profile in this patient population. Grade >3 treatment-related adverse events (TRAEs), which were predominantly hematologic toxicities, occurred in 85.1% of patients treated with iza-bren and 60.2% of patients who received chemotherapy. TRAEs that led to treatment discontinuation occurred in 2% of patients treated with iza-bren and 3.3% treated with chemotherapy. Treatment-related deaths occurred in 1.2% of patients treated with iza-bren and 1.6% of patients treated with chemotherapy. The rates of all grades and grade >3 ILD were low in the iza-bren arm (1.6%/0.8%) and the chemotherapy arm (0.4%/0.4%).
A New Drug Application for iza-bren for the treatment of recurrent or metastatic esophageal squamous cell carcinoma has been accepted by the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration (NMPA) and included in the priority review process.
The PANKU-Breast02 and PANKU-Esophagus01 studies are sponsored by SystImmune’s parent company, Sichuan Biokin Pharmaceutical Co., Ltd. (Biokin), in Mainland China. Outside of China, iza-bren is jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement.
About iza-bren
Iza-bren (BL-B01D1) is a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3, which are highly expressed in various epithelial cancers and are known to be associated with cancer cell proliferation and survival. Iza-bren’s dual mechanism of action blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. In addition, upon antibody mediated internalization, iza-bren’s therapeutic novel Topo1i payload is released causing cytotoxic stress that leads to cancer cell death.
(Press release, Bristol-Myers Squibb, JUN 2, 2026, View Source [SID1234666362])