Pumitamig Plus Chemo Yields Promising Efficacy in Advanced Triple-Negative Breast Cancer

The addition of the investigational PD-L1 x VEGF-A bispecific antibody pumitamig (BNT327/BMS986545) to chemotherapy produced responses when administered in the first- or second-line setting for patients with locally advanced or metastatic triple-negative breast cancer (TNBC), according to data from cohort 1 a phase 2 trial (NCT06449222).¹

Findings presented at the 2025 San Antonio Breast Cancer Symposium demonstrated that patients treated across both evaluated dose levels of pumitamig in combination with nab-paclitaxel (Abraxane; n = 39) achieved a confirmed overall response rate (ORR) of 61.5% (95% CI, 44.6%-76.6%) and an unconfirmed ORR of 71.8% (95% CI, 55.1%-85.0%). The unconfirmed best overall responses comprised partial response (71.8%), stable disease (23.1%), and progressive disease (5.1%). The disease control rate (DCR) was 92.3% (95% CI, 79.1%-98.4%), and the mean best percentage chance was –42.6% (standard deviation, 32.1). Early tumor shrinkage was observed in 66.7% (95% CI, 49.8%-80.9%) of patients.

Patients treated with pumitamig at a dose of 20 mg/kg (n = 20) experienced a confirmed ORR of 70.0% (95% CI, 45.7%-88.1%) and an unconfirmed ORR of 80.0% (95% CI, 56.3%-94.3%). In patients treated at a dose of 15 mg/kg (n = 19), the confirmed and unconfirmed ORRs were 52.6% (95% CI, 28.9%-75.6%) and 63.2% (95% CI, 38.4%-83.7%), respectively.

“Based on these global [first- and second-line] data, 20 mg/kg [of] pumitamig was selected as the dose for cohort 2 [as a flat-dose equivalent] and for further development of pumitamig in locally advanced/metastatic TNBC,” lead study author Peter Schmid, MD, PhD, FRCP, and colleagues wrote in a poster presentation of the data.

Schmid is a professor of cancer medicine, lead of the Centre of Experimental Cancer Medicine, and director of the Barts Breast Cancer Centre at Barts Cancer Institute in London.

How was the phase 2 trial of pumitamig designed?

After pumitamig plus nab-paclitaxel previously displayed encouraging activity in patients with first-line locally advanced/metastatic TNBC a phase 1 trial (NCT) conducted in China,² this phase 2 study sought to evaluate the combination on a global scale.¹

The global, randomized, open-label, multi-cohort phase 2 study enrolled patients at least 18 years of age with confirmed first- or second-line locally advanced/TNBC, irrespective of PD-L1 expression. Patients needed to have measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, adequate organ function, and a life expectancy of at least 3 months.

In cohort 1, patients were randomly assigned to receive pumitamig at 15 mg/kg once every 2 weeks or at 20 mg/kg once every 2 weeks, with both dose levels given in combination with standard-of-care nab-paclitaxel. In cohort 2, investigators evaluated pumitamig at 1400 mg once every 2 weeks in combination with paclitaxel; at 2000 mg once every 3 weeks in combination with gemcitabine and carboplatin; and at 2000 mg once every 3 weeks in combination with eribulin.

The trial’s primary end points were ORR per RECIST 1.1 criteria, best percentage change in tumor size per RECIST 1.1 criteria, early tumor shrinkage, and safety. Secondary end points included pharmacokinetics, ORR for cohort 2, duration of response, DCR, time to response, progression-free survival, and overall survival.

Notably, enrollment is ongoing in cohort 2, and follow-up time for this group was too short to evaluate efficacy end points at the October 1, 2025, data cutoff. At cutoff, the median follow-up was 33.6 weeks (range, 2.0-27.4) for cohort 1 and 13.2 weeks (range, 2.4-27.1) for cohort 2.

Patients treated at either dose level in cohort 1 (n = 40) had a median age of 57.1 years (range, 34-75). The majority had an ECOG performance status of 0 (67.5%) and received prior systemic therapy (57.5%); notably, most patients received prior therapy in the early-stage setting (55.0%) vs the metastatic setting (2.5%). Across the 3 arms of cohort 2 (n = 34), the median age was 51.0 years (range, 32-85), and most had an ECOG performance status of 0 (52.9%). Prior therapy was administered to 70.6% of patients in the early-stage setting (58.8%) or metastatic setting (11.8%).

What safety data were reported with pumitamig-based therapy in cohorts 1 and 2?

In cohort 1, any-grade treatment-emergent adverse effects (TEAEs) occurred in all patients, including 67.5% who had grade 3 or higher TEAEs. Treatment-related AEs (TRAEs) of any grade and grade 3 or higher occurred in 97.5% and 42.5% of patients, respectively. The rates of any-grade serious TEAEs and immune-related TEAEs were 42.5% and 20.0%, respectively. Any-grade TEAEs led to dose interruptions of any treatment in 40.0% of patients, dose reductions of chemotherapy in 27.5% of patients, discontinuation of any treatment in 7.5% of patients, and discontinuation of pumitamig in 7.5% of patients.

Across the 3 arms of cohort 2, the respective rates of any-grade and grade 3 or higher TEAEs were 91.2% and 38.2%. TRAEs of any grade were reported in 88.2% of patients, including 38.2% who had grade 3 or higher TRAEs. The rates of any-grade serious TEAEs and immune-related TEAEs were 14.7% and 5.9%, respectively. Any-grade TEAEs led to interruption of any treatment in 38.2% of patients, dose reductions of chemotherapy in 17.6% of patients, and discontinuation of any study treatment in 2.9% of patients. Notably, TEAEs did not led to discontinuation of pumitamig in any patients in cohort 2.

What was found in a ctDNA analysis of cohort 1 in the phase 2 trial?

At cycle 3, day 1, 17 patients in the 15-mg/kg group and 17 patients in the 20 mg/kg group were evaluable for circulating tumor DNA (ctDNA) dynamics, and the median ctDNA reduction at this time point vs baseline was 100% in both arms. The ctDNA clearance rate was 52.9% in the 15-mg/kg group and 70.6% in the 20-mg/kg group.

“Longitudinal ctDNA monitoring highlighted that distinct ctNA kinetics between treatment arms further sustains the higher efficacy of the higher dose of 20 mg/kg,” study authors wrote. “Deeper and durable ctDNA reduction [was] observed in patients receiving [pumitamig] at 20 mg/kg, regardless of best overall response. Although an initial ctDNA reduction was observed at the lower dose [of pumitamig], ctDNA levels rebounded for most patients with stable disease as best overall response.”

References

1. Schmid P, Williams A, Aksoy S, et al. Preliminary data from a global multicohort phase 2 randomized trial of pumitamig (PD-L1 x VEGF-A bsAb) + chemotherapy for 1L/2L+ locally advanced/metastatic TNBC. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract 3678.
2. Wu J, Zhang J, Tong Z, et al. Interim overall survival of patients with locally advanced or metastatic triple-negative breast cancer treated with first line PM8002/BNT327 in combination with nab-paclitaxel in phase Ib/II study. Clin Cancer Res. 2025;31(suppl 12):PS3-08. doi:10.1158/1557-3265.SABCS24-PS3-08