The EGFR and HER3 bispecific antibody–drug conjugate izalontamab brengitecan significantly improved progression-free survival vs chemotherapy in heavily pretreated Chinese patients with hormone receptor–positive, HER2-negative breast cancer, according to results from the multicenter phase III PANKU-Breast01 trial presented during the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract LBA50) and published by Lan et al in The Lancet.
“These results suggest that [izalontamab brengitecan] could be a new treatment option for this population in China; however, further evaluation of [izalontamab brengitecan] in global populations and in earlier lines of therapy for HER2-negative breast cancer is warranted,” the investigators wrote.
Study Details
The investigators focused on 383 female patients (median age = 54.0 years) with hormone receptor–positive, HER2-negative breast cancer who experienced disease progression following endocrine therapy, CDK4/6 inhibitor therapy, and one or two lines of chemotherapy at 72 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive izalontamab brengitecan or the physician’s choice of chemotherapy with eribulin, vinorelbine, gemcitabine, or capecitabine.
The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival in the modified intention-to-treat population, which included all randomly assigned patients who received at least one dose of study treatment.
Key Findings
At a median follow-up of 15.2 months, izalontamab brengitecan appeared to significantly improve progression-free survival compared with chemotherapy (log-rank P < .0001). Median BICR-assessed progression-free survival was 8.2 vs 4.0 months, respectively (hazard ratio [HR] = 0.41, 95% confidence interval = 0.33–0.53).
The overall survival data remained immature.
Grade 3 or higher treatment-related adverse events were reported in 85% of patients treated with izalontamab brengitecan vs 66% of those who received chemotherapy, with hematologic adverse events being the most common in both groups. In the izalontamab brengitecan group, 73% of patients received platelet-elevating agents, 15% received platelet transfusions, and 10% received blood transfusions to manage hematologic adverse events. Two patients treated with izalontamab brengitecan died because of treatment-related adverse events.
“Results of PANKU-Breast01 suggest izalontamab brengitecan could be a new treatment option for patients with heavily pretreated [hormone receptor–positive, HER2-negative] breast cancer and indicate the potential for future development of izalontamab brengitecan in global populations,” the investigators concluded. “Overall survival data are immature, and a longer follow-up is needed.”
Binghe Xu, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, is the corresponding author of the article in The Lancet.
Disclosure: The study was funded by Baili-Bio (Chengdu) Pharmaceutical, CAMS Innovation Fund for Medical Sciences, Noncommunicable Chronic Diseases–National Science and Technology Major Project, National High Level Hospital Clinical Research Funding, and the National Natural Science Foundation of China. For full disclosures of the study authors, visit thelancet.com.
