Dr Sammons on the Efficacy of Pumitamig in Advanced or Metastatic TNBC

“In this study, the ORRs were identical for the PD-L1–positive and PD-L1–negative populations, showing that we have hope for an immunotherapeutic strategy for our PD-L1–negative patients, who have not had that before.”

Sarah Sammons, MD, associate director of the Metastatic Breast Cancer Program and a senior physician at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, discussed efficacy findings from a phase 2 study (NCT06449222) investigating pumitamig (BNT327/IBI322), an investigational bispecific antibody targeting both PD-L1 and VEGF-A, in patients with locally advanced or metastatic triple-negative breast cancer (TNBC).

Sammons argued that although the current standard of care for metastatic TNBC limits immunotherapy to patients with PD-L1–positive disease who have not received prior immunotherapy, this leaves approximately two-thirds of the advanced TNBC patient population without an effective immunotherapeutic option. This unmet need served as the foundation for the global, multicohort, randomized phase 2 trial that evaluated the safety and efficacy of pumitamig in combination with various chemotherapy backbones in both the first- and second-line treatment settings.

According to Sammons, the global study validated previous data from China, confirming that pumitamig is an active agent. In cohort 1, which included 39 efficacy-evaluable patients receiving pumitamig plus nab-paclitaxel, the results were high for a population with mixed treatment lines. The confirmed objective response rate (ORR) was 61.5%, and the disease control rate was 92.3%. Sammons emphasized that the ORRs were identical between evaluable patients in the PD-L1–positive (n = 17) and –negative (n = 17) populations. PD-L1 positivity was defined as a combined positive score of at least, and both groups achieved an unconfirmed ORR of 70.6% This finding offers a breakthrough for the significant portion of patients who were previously excluded from immunotherapy strategies due to their PD-L1 status, she explained.

To supplement these efficacy findings, the research utilized circulating tumor DNA (ctDNA) dynamics to optimize dosing. Data from the study indicated that a 20-mg/kg dose of pumitamig led to a deeper and more durable reduction in ctDNA levels—with a 100% median reduction rate at the start of the third cycle—compared with the 15-mg/kg dose. Although treatment-related adverse effects (TRAEs) occurred in 97.5% of patients, the safety profile of pumitamig was considered manageable, with the most common grade 3 or higher TRAEs being hypertension (13.5%) and proteinuria (8.1%).