Abstract PS1-13-25: Preliminary data from a global multicohort Phase2 randomized trial of pumitamig (PD-L1 × VEGF-A bsAb) + chemotherapy for 1L/2L+ locally advanced/metastatic TNBC

Abstract Background: Pumitamig (BNT327/BMS986545) is an investigational bispecific antibody targeting PD-L1 and VEGF-A, designed to restore effector T-cell function through PD-L1 binding, while co-localizing VEGF-A neutralization to the tumor microenvironment. Pumitamig + nab-paclitaxel showed encouraging activity in a Phase 1b/2 trial of 1L locally advanced or metastatic triple-negative breast cancer (LA/mTNBC) in China (PS3-08, SABCS 2024). Herein we present the first pumitamig data from a global 1L/2L+ LA/mTNBC population. Methods: In this global Phase 2, randomized, open-label, multicohort trial (NCT06449222), Cohort 1 enrolled patients (pts) with 1L/2L+ LA/mTNBC (50% cap of 2L+ TNBC) who received pumitamig (15 or 20 mg/kg IV Q2W) + nab-paclitaxel until disease progression/unacceptable toxicity. In Cohort 2, pts received the flat dose equivalent of 20 mg/kg pumitamig IV: Arm 1: 1400 mg Q2W + paclitaxel; Arm 2: 2000 mg Q3W + gemcitabine + carboplatin; Arm 3: 2000 mg Q3W + eribulin. Primary endpoints were efficacy (ORR per investigator [RECIST 1.1], best percentage change in tumor size and early tumor shrinkage) and safety (NCI CTCAE v5.0). FoundationOne®Liquid CDx analysis estimated circulating tumor DNA (ctDNA) levels. Results: At cutoff (13 Aug 2025), 69 pts with 1L/2L+ TNBC were enrolled. Median duration of treatment (Tx) was 27.6 wks (range 2.0-41.0) with 27/40 pts still on Tx (Cohort 1) and 8.0 wks (range 3.0-20.4) with all pts on Tx (Cohort 2). In Cohort 1 (enrollment complete, median age: 57.1 yrs; 1L: 21 pts, 2L+: 19 pts), 19 pts received pumitamig 15 mg/kg and 21 pts received 20 mg/kg. In 39 efficacy-evaluable pts, unconfirmed best overall response was PR in 27 pts and SD in 9 pts for an uORR of 69.2% (1L: 71.4%; 2L+: 66.7%) and DCR of 92.3%. Confirmed ORR (cORR) was 56.4%. uORR was 63.2% with pumitamig 15 mg/kg (cORR 47.4%) and 75.0% with pumitamig 20 mg/kg (cORR 65.0%). Of 34 pts with centrally tested PD-L1 levels (22C3 pharmDx assay), 17 had CPS ≥10 (uORR: 70.6%) and 17 CPS