Editor's Note: At the 2026 European Society for Medical Oncology (ESMO) Congress, the PANKU-Breast01 study, led by Academician Binghe Xu of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, was presented as a late-breaking abstract (LBA) and simultaneously published in the internationally renowned medical journal The Lancet (impact factor: 109). In the more than 200-year history of The Lancet, this is the first study of an innovative Chinese drug in the breast cancer field to be published in the journal's flagship edition.As the world’s first-in-class, first approved, and most clinically impactful EGFR×HER3 bispecific ADC, iza-bren (BL-B01D1) achieved positive Phase III results in later-line treatment of HR+/HER2− breast cancer. This not only marks the arrival of the first bispecific ADC in this setting to demonstrate a positive primary endpoint, but also highlights the growing global leadership of China’s homegrown innovative medicines, marking a transition from following international advances to leading them. During the congress, Oncology Frontier invited Academician Binghe Xu to provide an in-depth interpretation of the clinical value and far-reaching significance of this landmark study.
Study Overview
Addressing Unmet Clinical Needs: The Enrolled Population Closely Reflects Real-World Difficult-to-Treat Disease
HR+/HER2− breast cancer is the most common molecular subtype of breast cancer, accounting for approximately 70% of all cases. Although first-line endocrine therapy combined with CDK4/6 inhibitors (CDK4/6i) has significantly improved patient outcomes, substantial unmet needs remain in later-line treatment after resistance to endocrine therapy and CDK4/6 inhibitors develops.
Iza-bren is the world’s first-in-class EGFR×HER3 bispecific antibody–drug conjugate (ADC), featuring a cleavable linker conjugated to a novel topoisomerase I inhibitor payload (Ed-04). Early Phase I study data have already demonstrated favorable efficacy and safety in patients with HR+/HER2− breast cancer who have received multiple prior lines of treatment.
PANKU-Breast01 was an open-label, randomized, controlled Phase III clinical study led by Academician Binghe Xu and conducted across 72 centers in China. It enrolled 383 patients with unresectable locally advanced or metastatic HR+/HER2− breast cancer who had previously received endocrine therapy and one to two lines of chemotherapy. Patients were randomized 1:1 to receive iza-bren (190 patients) or treatment of physician’s choice (TPC; 193 patients), which included eribulin, capecitabine, gemcitabine, or vinorelbine. Randomization was stratified according to the number of previous chemotherapy lines, central nervous system metastasis status, and HER2 expression level (IHC 0/1+/2+/ISH-negative). The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR), and the key secondary endpoint was overall survival (OS).
Baseline characteristics were balanced between the two groups, and the enrolled population closely reflected real-world clinical practice: 100% of patients had previously received CDK4/6 inhibitors; 80% had previously received (neo)adjuvant therapy and anthracyclines; 71.6% had liver metastases at baseline; and 64.2% had an ECOG performance status of 1. Overall, the population exhibited high-risk disease from an early stage, aggressive tumor biology, multiple prior lines of treatment in the advanced setting, and relatively poor performance status.
Doubling of Efficacy, Consistent Benefits Across Subgroups, and Deeper, More Durable Tumor Responses
The study met its prespecified primary endpoint. As of July 21, 2026, median PFS in the iza-bren group reached 8.2 months, twice that in the chemotherapy group (4.0 months), representing a 59% reduction in the risk of disease progression or death (HR=0.41, 95% CI: 0.33–0.53, P<0.0001).
The PFS curves separated significantly at an early stage of follow-up. The 6-, 9-, and 12-month PFS rates were 62.8% versus 24.2%, 41.8% versus 14.4%, and 26.5% versus 9.2%, respectively, consistently favoring iza-bren over chemotherapy.
Of particular importance, subgroup analyses confirmed consistent PFS benefits across all subgroups, prospectively demonstrating that the efficacy of iza-bren is independent of HER2 expression level, including IHC 0, IHC 1+, and IHC 2+/ISH-negative tumors. This finding challenges the limitations of traditional ADC treatment strategies that rely on HER2 expression-based patient stratification. The logic of clinical decision-making is shifting from “selecting treatment according to expression level” toward “making treatment decisions based on efficacy data.” Efficacy evidence, rather than HER2 expression level, is becoming the central consideration in treatment selection.
Regarding tumor response, the confirmed objective response rate (cORR) in the iza-bren group reached 40.5%, twice that in the chemotherapy group (20.2%). A reduction in target lesion size was observed in 77.9% of patients, with a median tumor shrinkage of 37.4%. Median duration of response (mDoR) was 6.9 months, longer than the 4.2 months observed in the chemotherapy group. These results demonstrate comprehensive benefits characterized by “higher response rates, deeper tumor shrinkage, and more durable responses.”
A Predictable Safety Profile, Low ILD Incidence, and Low Treatment Discontinuation Rate
The adverse event profile of iza-bren was predictable and consistent with previous studies, with no new safety signals identified. Treatment-related adverse reactions were primarily hematologic toxicities and could be effectively managed with standard supportive care.
The rate of permanent treatment discontinuation due to treatment-related adverse events was only 1.6%. Median treatment duration was 7.3 months, nearly three months longer than the 4.3 months in the chemotherapy group. These findings suggest that patients can tolerate prolonged treatment and maintain good treatment adherence.
Investigator Insights
Academician Binghe Xu: I am extremely pleased that we have been able to witness the presentation of the PANKU-Breast01 study as an LBA at this year’s ESMO Congress alongside colleagues from around the world. The results reflect the commitment and concern of Chinese researchers toward patients with difficult-to-treat HR+/HER2− breast cancer. They also represent another important step in bringing original research from China to the global stage.
A Novel Mechanism That Overcomes the Limitations of Single-Target Approaches at Their Source
As the world’s first-in-class EGFR×HER3 bispecific ADC, iza-bren is fundamentally different from conventional single-target ADCs. It can recognize and expand its coverage of heterogeneous tumor cells while optimizing intracellular payload delivery through dual-receptor binding. Its coordinated design, combining the linker and novel payload, enables the full cytotoxic potential of the drug to be realized.
This mechanistic innovation has translated into substantial clinical benefits: median PFS doubled to 8.2 months, with a 59% reduction in the risk of disease progression or death, while cORR doubled to 40.5%.
More importantly, the study enrolled a population characterized predominantly by high-risk, difficult-to-treat disease. From the outset, PANKU-Breast01 was not designed around the careful selection of low-risk patients. Instead, it directly addressed the needs of patients with advanced HR+/HER2− breast cancer, including those with a high burden of liver metastases and multiple prior treatment failures. The enrolled population therefore closely reflects real-world clinical practice.
Combining Efficacy and Safety to Simplify Clinical Decision-Making
The value of ADCs in later-line treatment of HR+/HER2− breast cancer is now widely recognized. However, treatment selection still requires careful consideration of efficacy, safety, and mechanism of action.
I have always believed that efficacy should be the primary consideration when selecting later-line treatments, followed by safety and mechanism of action.
PANKU-Breast01 confirmed that the efficacy of iza-bren is independent of HER2 expression level, with consistent benefits observed in the IHC 0, IHC 1+, and IHC 2+/ISH-negative subgroups. This means that clinicians do not need to repeatedly reassess HER2 status when making treatment decisions, simplifying the clinical decision-making pathway and potentially improving access to treatment.
Regarding safety, interstitial lung disease (ILD) is one of the most closely monitored adverse events associated with ADCs. In PANKU-Breast01, the incidence of ILD was only 1.1%, and all cases were Grade 1–2. The rate of permanent treatment discontinuation due to treatment-related adverse events was only 1.6%, comparable to that in the chemotherapy group.
This means that patients not only have access to a treatment option, but also have a potentially better treatment option that they can continue using over the long term. In this way, both efficacy and safety can be made accessible to patients.
From Chinese Innovation to Global Leadership: Ushering in a New Era of Bispecific ADC Therapy
Previously, many of the studies we conducted were primarily “following” international research developments. PANKU-Breast01, however, is a “leading” study. Before this trial, no bispecific ADC had been investigated as a treatment for patients with HR+/HER2− breast cancer.
Through high-quality, multicenter clinical evidence generated across China, PANKU-Breast01 has demonstrated to the world the rigorous standards of Chinese clinical research and the strong quality of innovative medicines developed in China.
We hope that this study, originating from Chinese patients and built on Chinese clinical practice, will eventually benefit more breast cancer patients worldwide and contribute Chinese expertise and strength to global cancer prevention and treatment.
Conclusion
PANKU-Breast01 once again confirms the breakthrough clinical value of iza-bren in breast cancer treatment. Its robust clinical data demonstrate the capabilities and clinical impact of this innovative ADC. Meanwhile, the drug’s clinical translation is accelerating. On October 21, 2026, information published by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration confirmed that the marketing application for iza-bren for HR+/HER2− breast cancer had been formally accepted. The proposed indication is for patients with unresectable locally advanced, recurrent, or metastatic HR+/HER2− breast cancer whose disease has progressed after at least one prior line of chemotherapy.
From showcasing “Chinese innovation” on the international stage to completing the “last mile” of clinical translation in China, iza-bren is accelerating the transformation of the advantages of bispecific ADC innovation into tangible patient benefits. It has the potential to provide better treatment options for patients with advanced HR+/HER2− breast cancer in China in the near future.
Academician Binghe Xu
