Abstract PD18-08: Efficacy and safety results of KN026, a HER2-targeted bispecific antibody combined with docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer
Authors: Zhang Qingyuan , Wang Jingxuan , Ouyang Quchang , Wang Xiaojia , Wang Jingfen , Gan Lu , Lin Daren , Ouyang Zhong , Xu Ting , Liu Yilan , Xia Summer 
Published: March 2023

Abstract
Background: 1. The 3-drug combination therapy, trastuzumab, pertuzumab, and taxane chemotherapy is one of the standard treatment options for the first-line treatment of HER2-positive recurrent/metastatic breast cancer. 2. KN026 is a novel bispecific HER2-targeted antibody : Fully humanized, IgG1-like antibody binds to two distinct HER2 epitopes, the same domains as trastuzumab (ECD4) and pertuzumab (ECD2). IgG1 Fc fragment of KN026 binding FcγRIIIa mediates potent ADCC 3. Preliminary safety and efficacy results from Phase 1 study data (data as of January 22, 2020) of KN026 monotherapy in HER2-positive advanced breast cancer were presented at ASCO 2020, showed promising efficacy and well tolerated safety. Herein, we present the results from the phase 2 trial. Methods:  Eligible subjects with HER2-positive and first-line systemic treatment-naïve (relapse ≥12 months after the end of neoadjuvant/adjuvant therapy) recurrent or metastatic breast cancer were enrolled in this study.  Subjects received KN026 30 mg/kg combined with docetaxel 75 mg/m2 Q3W until disease progression, unacceptable toxicity, withdrawal of informed consent from subjects, or other circumstances that require drug discontinuation.  The primary endpoints were ORR and duration of response (DoR). The secondary endpoints included safety, PFS and OS. Results:  At data cut-off date (Mar 26, 2022), the median follow-up was 13.8 months (Interquartile Range [IQR] 12.22, 14.00). 57 subjects were enrolled, the median age was 52 years, 100% were female, and 89.5 % (51/57) were stage IV.  Of the 55 subjects evaluable for efficacy, 21 had received prior taxane, 4 had received prior trastuzumab in combination with taxane, 30 without any prior trastuzumab and taxane. Nearly half of the subjects (25/55) had previously received trastuzumab and/or taxane chemotherapy.  The confirmed ORR within 55 evaluable subjects was 76.4% (95% CI: 62.98, 86.77) and DoR was 18.1 months (95% CI: 12.45, NE).  Median PFS was 19.3 months (95% CI: 13.86, NE) and median OS was not reached. Median PFS is not yet mature. The 12-, and 18-month OS rates were 93.5% (95% CI: 80.79, 97.89), and 88.3 % (95% CI: 68.93, 95.92), respectively.  The confirmed ORR was 80% in 30 trastuzumab-and taxane-naïve subjects. Among these subjects, OS rates at 12, and 18 months were 100% (95% CI: 100,100), and 90.0% (95% CI: 47.30, 98.53), and the median PFS was 19.3 months (95% CI:13.77, NE).  Treatment emergent adverse events with incidence rate ≥20% and TEAE≥Grade 3 were neutropenia (n=23, 40.4%) and leucopenia (n=16, 28.1%), respectively.  The incidence of serious adverse events was 15.8%(9/57), including 5.3% (3/57) for febrile neutropenia, 3.5% (2/57) for leucopenia, and less than 2% for other SAEs  There were no deaths due to KN026 drug-related AEs in this study. Conclusions: KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as a 1L treatment for HER2-positive advanced breast cancer. At data cut-off date (Mar 26, 2022), median PFS was 19.3 months while 18-month OS rate was 88.3%, which is very encouraging. Efficacy and safety require large-scale phase III studies to verify.
Citation Format: Qingyuan Zhang, Jingxuan Wang, Quchang Ouyang, Xiaojia Wang, Jingfen Wang, Lu Gan, Daren Lin, Zhong Ouyang, Ting Xu, Yilan Liu, Summer Xia. Efficacy and safety results of KN026, a HER2-targeted bispecific antibody combined with docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-08.