Abstract PS1-08-05: First disclosure of efficacy and safety data for YL202/BNT326 (HER3 antibody-drug conjugate [ADC]) in advanced or metastatic HR+/HER2 null and HER2-low breast cancer: Phase 2 trial results

Abstract Background: YL202/BNT326 is an investigational ADC composed of an anti-HER3 IgG1 monoclonal antibody conjugated to ∼8 molecules of a novel topoisomerase I inhibitor payload via a tripeptide linker. This phase 2 trial evaluates YL202/BNT326 monotherapy in patients (pts) with locally advanced or metastatic breast cancers (BC). Here, we report data from hormone receptor positive (HR+) BC patients with HER2 null (including HER2-ultralow) or HER2-low expression. Methods: In this Phase 2 trial (NCT06439771) conducted in China, pts with HR+ and HER2-null expression (HER2 no expression, HER2 ultralow expression [0 < IHC < 1+]) and HER2-low expression (IHC score of 1+, 2+/ISH-) who had received ≥1 prior CDK4/6 inhibitor, prior endocrine therapy, and 0-4 lines of prior chemotherapy were treated with 2.0, 2.5, or 3.0 mg/kg YL202/BNT326 Q3W. Primary endpoints are objective response rate (ORR), based on investigator assessment per RECIST 1.1, and recommended dose. Secondary endpoints include safety, disease control rate (DCR), duration of response, progression-free survival, and overall survival. Results: As of 1 September, 2025, 75 pts had received ≥1 dose of YL202/BNT326; 49 pts remain on treatment. Median age was 55.5 years, all pts were Asian, and the majority had ECOG PS 1 (73.3%). HER2 expression per local testing was HER2-low in 46 pts and HER2-null in 29 pts. Efficacy data (summarized in the table) is available for all 75 pts after a median follow-up of 5.5 months. More mature and additional data will be presented at the conference. Treatment-emergent adverse events occurred in 71 (94.7%) pts. Treatment-related adverse events (TRAEs) occurred in 70 pts (93.3%), with Grade ≥3 in 14 pts (18.7%). TRAEs led to dose reduction in 11 pts (14.7%). No dose discontinuation or deaths resulted from TRAEs. The most common TRAEs of any grade included decreased white blood cell count (57.3%), anemia (52%), decreased neutrophil count (50.7%), and nausea (34.7%). TRAEs of grade 3 or higher were less frequent, with decreased neutrophil count (8.0%), anemia (5.3%), and decreased white blood cell count (4.0%) being the most notable. Conclusions: The data suggest an encouraging clinical efficacy and manageable safety profile of YL202/BNT326 in BC pts with HR+ and HER2 null or HER2-low expression, with no treatment discontinuation due to TRAEs. This study continues to enroll pts with HR+ HER2-null/low BC and in addition is enrolling pts with triple-negative breast cancer. Furthermore, YL202/BNT326 is being evaluated in combination with pumitamig, an investigational anti-PD-L1 x VEGF-A bispecific antibody in pts with BC (NCT07070232). Citation Format: J. Zhang, Y. Meng, L. Cai, T. Wu, T. Sun, H. Li, Q. Ouyang, F. Xu, C. Trück, M. Wenger, R. Tibes, N. Wang, J. Bai, S. Chin. First disclosure of efficacy and safety data for YL202/BNT326 (HER3 antibody-drug conjugate [ADC]) in advanced or metastatic HR+/HER2 null and HER2-low breast cancer: Phase 2 trial results [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-08-05.