At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Jiong Wu from Fudan University Shanghai Cancer Center presented the highly anticipated PANKU-Breast02 study (Abstract LBA1003).PANKU-Breast02 is a randomized, multicenter, open-label Phase III trial evaluating Iza-Bren, a first-in-class EGFR×HER3 bispecific antibody-drug conjugate (ADC), versus physician’s choice of chemotherapy in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who had received one or two prior lines of systemic therapy.
The trial met both of its co-primary endpoints. Median progression-free survival (PFS) was 8.5 months with Iza-Bren versus 3.1 months with chemotherapy (HR=0.29; P<0.0001), while median overall survival (OS) improved from 12.5 months to 15.9 months (HR=0.60; P=0.0019), successfully surpassing the predefined superiority threshold. These findings represent the first major breakthrough for a bispecific ADC in the later-line treatment of advanced TNBC and provide an important foundation for future combination strategies.
At the ASCO meeting, Oncology Frontier invited Jiong Wu to discuss the study in greater detail.
Oncology Frontier: Congratulations on the PANKU-Breast02 study achieving positive results for both PFS and OS. Could you briefly introduce the rationale and design of this Phase III trial? Why were both PFS and OS selected as co-primary endpoints? Could you also highlight the key efficacy findings and describe which patients benefited most?
Jiong Wu:
Triple-negative breast cancer remains one of the most challenging breast cancer subtypes because it lacks well-defined therapeutic targets and is highly aggressive. After progression on first-line immunotherapy combined with chemotherapy, treatment options remain limited. Patients whose disease progresses following taxane-based therapy generally have a poor prognosis, representing a significant unmet clinical need.
Iza-Bren is a first-in-class bispecific ADC targeting EGFR and HER3, carrying a potent topoisomerase I inhibitor payload. Early clinical studies demonstrated encouraging antitumor activity in breast cancer together with a manageable safety profile.
PANKU-Breast02 is a randomized, multicenter, open-label Phase III study enrolling patients with unresectable locally advanced or metastatic TNBC who had received one or two prior systemic treatment regimens for advanced disease, including previous taxane therapy. Patients were randomized 1:1 to receive either Iza-Bren at 2.5 mg/kg on Days 1 and 8 of every 3-week cycle or physician’s choice of chemotherapy, consisting of eribulin, capecitabine, gemcitabine, or vinorelbine.
Randomization was stratified according to the number of prior treatment lines (one versus two), previous anti-PD-(L)1 therapy, and HER2 immunohistochemistry status (IHC 0 versus IHC 1+/2+ with ISH negativity). The co-primary endpoints were progression-free survival, as assessed by blinded independent central review (BICR), and overall survival.
A total of 418 patients were randomized, with 412 receiving study treatment. At the data cutoff on January 13, 2026, the median follow-up was 11.0 months.
The median PFS assessed by BICR was 8.5 months in the Iza-Bren arm compared with 3.1 months in the chemotherapy arm (HR=0.29; 95% CI, 0.22–0.38; P<0.0001). Median OS was 15.9 months versus 12.5 months, respectively (HR=0.60; 95% CI, 0.42–0.85; P=0.0019). The confirmed objective response rate was also markedly higher with Iza-Bren, reaching 51.7%, compared with 20.5% in the chemotherapy group.
Regarding overall survival, the number of observed events differed somewhat from our original expectations. The protocol specified an interim analysis once approximately 70% of the planned OS events had occurred, but at the data cutoff, only 53% of the anticipated events had been observed. This likely reflects the growing availability of effective subsequent therapies, which has prolonged survival and delayed event accumulation.
Importantly, the statistical boundary for superiority had been set very stringently, requiring a P value below 0.0021. The observed P value of 0.0019 successfully crossed that threshold, confirming a statistically significant OS benefit consistent with the PFS findings.
We were therefore delighted to see PANKU-Breast02 achieve positive results for both co-primary endpoints at the preplanned interim analysis, which was one of the key reasons the study was selected for presentation in the Late-Breaking Abstract (LBA) session at this year’s ASCO meeting.
Oncology Frontier: Alongside these efficacy improvements, how did Iza-Bren perform in terms of safety? How does its adverse event profile compare with physician’s choice of chemotherapy?
Jiong Wu:
From a safety perspective, Grade 3 or higher hematologic toxicities occurred more frequently with Iza-Bren, but they were generally predictable and manageable.
The most common Grade ≥3 treatment-emergent adverse events were decreases in neutrophil count (58.0% vs. 46.8%), white blood cell count (56.0% vs. 33.2%), platelet count (52.7% vs. 2.4%), and anemia (46.9% vs. 3.9%) in the Iza-Bren and chemotherapy groups, respectively.
With standard supportive care and appropriate dose management, however, most patients were able to continue treatment. Discontinuation due to treatment-emergent adverse events remained uncommon, occurring in only 1.9% of patients receiving Iza-Bren and 0.5% of those receiving chemotherapy. Importantly, no new safety signals were identified.
Interstitial lung disease (ILD), a toxicity of particular concern with ADC therapies, was also closely monitored. In the Iza-Bren arm, all-grade ILD occurred in 1.4% of patients (three cases), all of which were Grade 1 or 2, with no Grade 3 or higher ILD reported.
Overall, the safety profile of Iza-Bren was considered favorable and manageable, supporting its potential as a new treatment option for patients with previously treated advanced TNBC.
Expert Profile
Jiong Wu
Fudan University Shanghai Cancer Center
