Abstract P5-16-04: Preliminary safety and efficacy results of KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) in combination with KN026 (a HER2-targeted bispecific antibody) in patients with metastatic HER2-positive breast cancer: A phase II trial
Authors: Liu Jieqiong , Song Chuangui , Wang Xiangcai , Ni Mingli , Wang Xujuan , Chen Lei , Yang Hongwei , Zhao Rusen , Xu Ting , Shen Lin 
Published: March 2022

Abstract
Background: HER2-targeted therapies combined with chemotherapy have improved survival outcomes for patients with metastatic HER2-positive breast cancer. However, for patients progressed after several lines of anti-HER2 combinational therapies, the overall survival (OS) remained unfavorable. Prior studies showed that immunotherapy in combination with chemotherapy or targeted therapy could significantly prolong OS of metastatic breast cancer patients, especially in patients with triple-negative breast cancer. Reports of immunotherapy combined with HER2-targeted therapy are still limited. Here we reported the preliminary results from an ongoing phase II trial assessing the safety and efficacy for KN046 (a bispecific antibody blocks both PD-L1 interaction with PD-1/CD80 and CTLA-4 interaction with CD80/CD86) in combination with KN026 (a bispecific antibody that binds to two different HER2 epitopes shared by trastuzumab and pertuzumab) in HER2-positive metastatic breast cancer patients, who have progressed after prior anti-HER2 combinational therapies.Methods: Female patients with metastatic HER2-positive breast cancer who were previously treated with at least one line of HER2-targeted combinational 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 Q6W per RECIST 1.1. The primary endpoint was objective response rate (ORR). Results: As of the June 20th, 2021, 36 patients with the median age of 53 years (range: 33-67) were enrolled. 30 of 36 patients (83.3%) received ≥3 lines of HER2-targeted combinational therapies in the metastatic setting. 22 patients were evaluable for overall response and all 36 for safety. The ORR was 50.0% (11 of 22, 95% CI: 28.2-71.8), and one patient achieved complete response (CR). And the disease control rate (DCR) was 81.8% (18 of 22, 95% CI 59.7-94.8). The median progression-free survival (PFS) was 5.6 (95%CI 2.5-not reached) months. 34 of 36 (94.4%) patients had treatment-related adverse events (TRAEs) of any grade, while 4 of 36 (11.1%) patients had experienced ≥grade 3 TRAEs. The most common (≥10%) TEAEs were infusion related reaction (36.1%), rash (16.7%), alanine aminotransferase increased (13.9%), diarrhea (13.9%), pruritus (13.9%), aspartate aminotransferase increased (11.1%), and hypokalemia (11.1%). No treatment-related deaths were observed.Conclusions: The combination of KN046 and KN026, as a chemo free regimen, has shown favorable clinical efficacy with manageable side effects in heavily pre-treated patients with metastatic HER2-positive breast cancer. This trial is currently ongoing. ClinicalTrials.gov number, NCT04521179.
Citation Format: Jieqiong Liu, Chuangui Song, Xiangcai Wang, Mingli Ni, Xujuan Wang, Lei Chen, Hongwei Yang, Rusen Zhao, Ting Xu, Lin Shen. Preliminary safety and efficacy results of KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) in combination with KN026 (a HER2-targeted bispecific antibody) in patients with metastatic HER2-positive breast cancer: A phase II trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-04.