Introduction: As the world's first approved EGFR × HER3 bispecific antibody–drug conjugate (ADC), Izecom (izalontamab brengitecan, BL-B01D1/iza-bren) features a dual-target structure designed to overcome the limitations associated with low or heterogeneous expression of a single target. It has demonstrated remarkable antitumor activity across multiple tumor types. The phase III PANKU-Breast02 study, jointly led by Professor Jiong Wu and Professor Jian Zhang of Fudan University Shanghai Cancer Center, reported positive results for both primary endpoints, progression-free survival (PFS) and overall survival (OS), in a high-profile late-breaking abstract (LBA) presentation at ASCO. In recognition of its breakthrough clinical value, the study also received the 2026 Innovative Research Award at this year's CSCO Annual Meeting. These achievements indicate that the clinical value of izalontamab brengitecan in breast cancer is attracting global attention and recognition.Ahead of the 18th Shanghai Breast Reconstruction Conference, Oncology Frontier invited Professor Jiong Wu of Fudan University Shanghai Cancer Center, the study’s principal investigator (PI), to share his insights into the structural advantages of bispecific ADCs, the key findings from PANKU-Breast02, and the potential impact of this treatment on the breast cancer landscape.
Oncology Frontier: Over the course of breast cancer treatment development, ADCs have become one of the standard treatment options for patients with advanced disease and are now widely used in clinical practice. The PANKU-Breast series of studies of izalontamab brengitecan has made considerable progress in breast cancer, and the marketing application for its triple-negative breast cancer (TNBC) indication has been accepted by China’s National Medical Products Administration (NMPA). Approval may be granted in the first half of next year. To begin, could you explain the advantages of izalontamab brengitecan over conventional single-target ADCs? What role do you anticipate it will play following market approval?
Professor Jiong Wu: In breast cancer, ADCs are expanding beyond salvage treatment for patients with recurrent or metastatic disease into neoadjuvant therapy and intensified adjuvant treatment. Target exploration is also moving beyond single targets such as HER2 and TROP2 toward new approaches involving multiple targets. Izalontamab brengitecan is an EGFR × HER3 bispecific ADC that offers new treatment hope for patients across different breast cancer subtypes.
From a structural design perspective, izalontamab brengitecan has three major advantages over conventional single-target ADCs.
First, dual-target binding enables potent tumor suppression. The drug can bind to EGFR and/or HER3. Dual-target binding further enhances receptor clustering, internalization, and payload delivery. At the same time, blocking both EGFR and HER3 signaling pathways may effectively overcome compensatory resistance mediated by bypass pathways.
Second, a stable linker enables precise payload release. The drug uses a proprietary, patented Ac stabilizing linker and a GGFG tetrapeptide linker. These components provide high stability in plasma, while the payload is released precisely through lysosomal enzyme-mediated cleavage after the ADC enters tumor cells. Its high drug-to-antibody ratio (DAR ≈ 8) substantially increases the effective drug concentration within the tumor.
Third, a novel payload delivers potent tumor killing. The payload, Ed-04, is a novel topoisomerase I inhibitor. Once released inside cells, it can exert its cytotoxic effects more effectively, producing stronger local killing of heterogeneous tumor cell populations within the tumor.
From a clinical evidence perspective, izalontamab brengitecan achieved positive results for both PFS and OS in the PANKU-Breast02 study, providing a new treatment option for patients with advanced metastatic triple-negative breast cancer (mTNBC) who have previously received one or two lines of chemotherapy. I also hope that its TNBC indication will receive NMPA approval as soon as possible, allowing this first-in-class bispecific ADC to benefit a broader population of Chinese patients at an earlier stage.
Oncology Frontier: The PANKU-Breast02 study, which you led, presented its findings at ASCO 2026 and subsequently received the Innovative Research Award at CSCO. Its positive results for both primary endpoints, PFS and OS, have earned recognition from experts in China and internationally. Based on the study data, how do you think these findings will change clinical practice in later-line treatment of mTNBC?
Professor Jiong Wu: PANKU-Breast02 enrolled patients with mTNBC who had previously received one or two lines of chemotherapy. These patients had a substantial disease burden and limited treatment options remaining. The study results showed the following.
Positive Results for Both Endpoints Set a New Benchmark for Survival Benefit in a Phase III Trial of Second-Line TNBC
Median PFS in the izalontamab brengitecan group reached 8.5 months, significantly exceeding the 3.1 months observed in the chemotherapy group. The absolute PFS benefit was 5.4 months (HR = 0.29; P < 0.0001), corresponding to a 71% reduction in the risk of disease progression or death.
Median OS was 15.9 months in the izalontamab brengitecan group, compared with just 12.5 months in the chemotherapy group (HR = 0.60; P = 0.0019), representing a 40% reduction in the risk of death.
This therapeutic breakthrough is particularly significant for patients with mTNBC. As a monotherapy, izalontamab brengitecan can significantly delay disease progression and prolong overall survival, offering renewed hope for patients in this challenging clinical setting.
A Clearly Characterized, Predictable, and Manageable Safety Profile
Regarding safety, most adverse events associated with izalontamab brengitecan were predictable and manageable. Hematologic toxicities, for example, occurred less frequently over subsequent treatment cycles with effective management, and their severity gradually decreased.
The median number of treatment cycles in this study exceeded eight. This not only provides evidence supporting the efficacy of izalontamab brengitecan but also indicates that its safety profile can be managed in clinical practice.
Interstitial lung disease (ILD), an adverse event of particular concern to clinicians, was confirmed by the independent assessment committee in only one patient (0.9%) in the izalontamab brengitecan group, and the case was mild. Overall, the drug demonstrated a favorable profile in terms of efficacy, safety, and patient management.
Oncology Frontier: Izalontamab brengitecan is a China-originated innovation and the world’s first EGFR × HER3 bispecific ADC. Its clinical development program covers all molecular subtypes of breast cancer and multiple lines of treatment. How should China-originated innovative medicines, including bispecific ADCs, expand internationally, and what impact could they have on the global breast cancer treatment landscape?
Professor Jiong Wu: Izalontamab brengitecan is a China-originated, first-in-class EGFR × HER3 bispecific ADC, and the data from its studies have been generated in Chinese patient populations. In recent years, I have witnessed firsthand the growing attention that many innovative biopharmaceutical products developed in China are receiving from colleagues around the world. Some products have embarked on international commercialization strategies at very early stages and are conducting important clinical studies globally.
When data from China are complemented and combined with global clinical data, the resulting evidence can benefit Chinese patients while also bringing substantial advantages to breast cancer patients worldwide. From another perspective, this progress also demonstrates the strong momentum of China’s biopharmaceutical innovation sector and the growing international recognition it has achieved.
Conclusion
Rooted in China, Expanding Globally: Continued Progress Across Multiple Tumor Types
The clinical development of izalontamab brengitecan continues to expand. Following its initial approvals for recurrent or metastatic nasopharyngeal carcinoma and esophageal squamous cell carcinoma, marketing applications for two additional indications—TNBC and EGFR-mutated non-small cell lung cancer (NSCLC) following failure of EGFR tyrosine kinase inhibitor (TKI) treatment—have been accepted by China’s Center for Drug Evaluation (CDE). The latter indication has also been granted priority review and approval status.
Notably, the drug’s development program across multiple tumor types has achieved progress on several fronts. Encouraging efficacy signals have been observed in solid tumors including lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, biliary tract cancer, and ovarian cancer. Nine indications have been included in the CDE’s Breakthrough Therapy Designation list.
This broad potential is supported by the relatively high expression of EGFR and HER3 across multiple solid tumors. Because izalontamab brengitecan does not depend on target testing for its use, it may offer broad activity across different solid tumors and potentially benefit a wider population of patients with cancer.
At the upcoming ESMO Congress, PANKU-Breast01—a pivotal phase III registration study led by Academician Binghe Xu of the Cancer Hospital, Chinese Academy of Medical Sciences, in patients with advanced HR-positive/HER2-negative breast cancer—has also been selected for an LBA presentation. The detailed findings are highly anticipated. Stay tuned!
Professor Jiong Wu
