Abstract PO1-29-02: Two and a half years follow-up data of HER2-targeted bispecific antibody KN026 combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer

Abstract Background: KN026 is a novel bispecific HER2-targeted antibody. Fully humanized, IgG1-like antibody binds to two distinct HER2 epitopes, the same domains as trastuzumab and pertuzumab. Preliminary safety and efficacy results (data as of Aug 18, 2022) were presented at SABCs 2022(PD18-08), showed promising efficacy and tolerability. Herein, we update the 2.5-year follow-up results. Methods: Eligible subjects with recurrent/metastatic breast cancer, HER-2 positive and treatment-naive were enrolled. Subjects received KN026 30 mg/kg combined with docetaxel 75 mg/m2 Q3W until disease progression, unacceptable toxicity, or other reasons. The primary endpoints were ORR and DoR. The secondary endpoints included safety, PFS and OS. Results: As of data cut-off date (Sep 15, 2023), 57 subjects were enrolled, the median age was 52 years (min:30, max:67), 100% were female, and 91.2 % (52/57) were stage IV. There were 34 and 23 subjects with and without visceral metastasis, respectively. 48 subjects with high HER2 expression (IHC 3+), and the other 9 subjects with HER2 expression 2+ or 1+. The confirmed ORR within 55 evaluable subjects was 76.4% (42/55). The DoR was not reached yet with a median follow-up of 27.0 mons (95% CI: 26.28, 28.98). The median study follow-up was 30.6 mons (95% CI: 29.11, 31.77). The mPFS was 27.7 mons (95% CI:17.97, NE) and the mOS was not reached. The OS rates at 12m, 24m and 30m were 93.0% (95% CI: 82.37, 97.31), 84.2% (95% CI: 71.85, 91.45) and 78.5% (95% CI: 65.25, 87.21). The mPFS of subjects with or without visceral metastasis were 23.6 mons and not reached. The mPFS of subjects with or without brain metastasis were 13.7 mons and 28.1 mons, respectively. The mPFS of 48 subjects with high HER2 expression (3+) was 28.1 months. The incidence of KN026-related Grade≥3 TRAE was 43.9% (25/57), including neutrophil count decreased 24.6% (14/57), white blood cell count decreased 12.3% (7/57), hypokalaemia 7.0% (4/57), diarrhoea 3.5% (2/57) and others less than 2%. The incidence of serious adverse events related to KN026 was 12.3% (7/57). There was no KN026 -related death. Conclusions: KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as 1L treatment for HER2-positive BC. After 2.5 years follow-up, mPFS was 27.7 mons and the 24-months OS rate was 84.2%, which is very promising. No new safety signals were observed. Robustness of efficacy and safety results will be further confirmed in an ongoing randomized phase 3 clinical trial with PTH as control. Citation Format: Qingyuan Zhang, Jingxuan Wang, Quchang Ouyang, Xiaojia Wang, Jingfen Wang, Lu Gan, Daren Lin, Zhong Ouyang, Ting Xu, Yilan Liu, Yuan Lv. Two and a half years follow-up data of HER2-targeted bispecific antibody KN026 combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-29-02.