Bispecific ADC May Offer New Treatment Option for HR-Positive, HER2-Negative Breast Cancer

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.