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 <10 (uORR: 64.7%). The mean best percentage change in tumor size was -40.5% with 66.7% of pts achieving early tumor shrinkage. In Cohort 2 (enrollment ongoing, median age: 53.5 yrs, 1L: 9 pts, 2L+: 20 pts), 29 pts received pumitamig + chemotherapy (n=8, Arm 1; n=10, Arm 2; n=11, Arm 3). In 17 efficacy-evaluable pts, uORR/DCR was 64.7%/88.2% (80.0%/80.0% in Arm 1 [n=5], 71.4%/100% in Arm 2 [n=7], 40.0%/80.0% in Arm 3 [n=5]). Updated efficacy, including early DOR and PFS, will be presented. In Cohort 1, baseline (BL) ctDNA detection rate was 94.7% (36/38 pts with cfDNA data), with median maximum allele fraction (mMAF) of 12.5%. At C3D1, mMAF change from BL in 34 evaluable pts was -100%. ctDNA clearance rate was 53% (9/17) for 15 mg/kg and 71% (12/17) for 20 mg/kg pumitamig. Similar results were observed in Cohort 2. Adverse events (AEs) related to either pumitamig or chemotherapy were reported in 39/40 (97.5%) and 23/29 [79.3%] pts, and were Grade ≥3 in 18 (45.0%) and 9 (31.0%) pts in Cohort 1 and Cohort 2, respectively. Pumitamig-related Grade ≥3 AEs were reported in 11 (27.5%) pts in Cohort 1 (5/19 [26.3%] pts receiving 15 mg/kg and 6/21 [28.6%] pts receiving 20 mg/kg) and in 4 (13.8%) pts in Cohort 2. One pt discontinued due to pumitamig-related AEs. No Tx-related deaths occurred. Conclusions: Pumitamig + chemotherapy showed encouraging efficacy independent of CPS levels and manageable safety in 1L/2L+ LA/mTNBC. The efficacy is particularly clinically meaningful in pts with CPS <10, addressing a critical unmet need. No new safety signals were seen compared to previously characterized safety profile of pumitamig. These global 1L/2L+ data align with the 1L TNBC Chinese trial and support further development of pumitamig in LA/mTNBC, being evaluated in the global ROSETTA Breast-01 Phase 3 trial (NCT07173751). Citation Format: P. Schmid, A. Williams, S. Aksoy, M. L. Telli, S. Loi, E. Papadimitraki, G. Vidal, Ö. Ateş, J. Vijayakumar, L. Pan, S. Koseoglu, C. Dalle Fratte, C. Pütter, D. Akahara, C.-N. Gann, P. Rietschel, C. Brus, Ö. Türeci, U. Şahin. 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]. 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 PS1-13-25.