418P Two-year follow-up data on the efficacy and safety of KN026, a HER2-targeted bispecific antibody combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer

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-year follow-up results. 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. As of data cut-off date (Mar 10, 2023), 57 subjects were enrolled, the median age was 52 y (min:30, max:67), 100% were female, and 91.2 % (52/57) were stage IV. The confirmed ORR within 55 evaluable subjects was 76.4% (42/55) and DoR was 24.0m (95% CI 20.27, NE). The median study follow-up was 24.2m (95%CI:22.80, 25.56). The mPFS was 25.4m (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), 83.7% (95% CI:70.97, 91.19) and 83.7% (95% CI:70.97, 91.19). The mPFS of subjects with or without visceral metastasis were 23.6m and 28.1m. The mPFS of subjects with or without brain metastasis were 13.7m and 25.4m, respectively. The incidence of KN026-related Grade≥3 TRAE was 38.6% (22/57), including neutrophil count decreased 26.3% (15/57), leucopenia 24.6% (14/57), alanine aminotransferase increased 14.0% (8/57) and others less than 10%. The incidence of serious adverse events was 19.3% (11/57), including febrile neutropenia 5.3% (3/57), leucopenia 3.5% (2/57), and others ≤ 2%. There was no KN026 -related death. KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as 1L treatment for HER2-positive BC. After 2 years follow-up, mPFS was 25.4m and the 30-m OS rate was 83.7%, which is very promising. Robustness of efficacy and safety results will be further confirmed in an ongoing randomized phase 3 clinical trial with PTH as control.