What question did this study set out to answer?

The aim is to assess the efficacy and safety of pumitamig combined with chemotherapy in patients with locally advanced or metastatic triple-negative breast cancer (TNBC).

February 19, 2026

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

Key Points

The aim is to assess the efficacy and safety of pumitamig combined with chemotherapy in patients with locally advanced or metastatic triple-negative breast cancer (TNBC).
Conducted a global Phase 2, randomized, open-label, multicohort trial.
Enrolled patients with 1L/2L+ locally advanced/metastatic TNBC who received treatment until disease progression or unacceptable toxicity.
Primary endpoints included overall response rate (ORR) and safety assessments.
Among 69 enrolled patients, the unconfirmed overall response rate (uORR) was 69.2%, with a confirmed ORR (cORR) of 56.4%.
Median treatment duration was 27.6 weeks for Cohort 1 and 8.0 weeks for Cohort 2.
Circulating tumor DNA (ctDNA) clearance rates were 53% for 15 mg/kg and 71% for 20 mg/kg pumitamig, indicating treatment effectiveness.
Most adverse events were reported as manageable, with no treatment-related deaths.

Abstract

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.

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Cite This Study

Schmid et al. (Tue,) studied this question.

synapsesocial.com/papers/6996a8e3ecb39a600b3f00fe https://doi.org/https://doi.org/10.1158/1557-3265.sabcs25-ps1-13-25

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