Safety and Efficacy of KN046 in combination with KN026 in Patients with advanced HER2-positive Breast Cancer: a Phase II Trial

Abstract

Purpose: Here we reported the results from a phase II trial assessing the safety and efficacy of KN046 in combination with KN026 in HER2-positive metastatic breast cancer patients, who had progressed after prior anti-HER2 combination therapies. Patients and Methods: Female patients with metastatic HER2-positive breast cancer who were previously treated with at least one line of HER2-targeted combination therapy were enrolled from multiple academic hospitals in China to receive KN046 (iv. 5 mg/kg Q3W) plus KN026 (iv. 30 mg/kg Q3W) until progression, unacceptable toxicities or patient withdrawal. Efficacy was evaluated every 6 weeks per RECIST 1.1. The primary endpoint was objective response rate (ORR). Results: A total of 36 patients with the median age of 53 years were enrolled. 30 of 36 patients (83.3%) received ≥3 lines of HER2-targeted combination therapies in the metastatic setting. Thirty-three patients were evaluable for overall response, and all 36 for safety. The ORR was 47.2% ( 95% CI: 30.4-64.5), with two patient achieving CR. The median PFS was 5.6 (95% CI 4.1-13.8) months. 34 of 36 (94.4%) patients experienced TRAEsof any grade, and 10 of 36 (27.8%) patients had experienced ≥grade 3 TRAEs. The most common TRAEs were infusion-related reaction (36.1%), rash (16.7%), alanine aminotransferase increased (13.9%), diarrhea (13.9%), pruritus (13.9%). No treatment-related deaths were observed. Conclusions: The combination of KN046 and KN026, as a chemo free regimen, demonstrated favorable clinical efficacy with comparative toxicities in pre-treated patients with advanced HER2-positive breast cancer.