Study of Pumitamig as an adjunct to chemotherapy in triple-negative breast cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue in which cells in the breast multiply uncontrollably. Treatment depends on various factors, including the patient’s overall health, the stage of the disease, and the tumor’s biological characteristics, such as the presence of hormone receptors (hormone receptor-positive) and HER2 status. In triple-negative breast cancer (TNBC), in which the tumor cells lack receptors for the hormones estrogen and progesterone and rarely express the human epidermal growth factor receptor 2 (HER2) on their cell surface, therapies targeting these hormone and HER2 receptors are ineffective. Therefore, chemotherapy is typically used as the standard treatment. This study is investigating the antibody drug Pumitamig (BNT327), which belongs to the class of bispecific antibodies. This antibody is designed to bind simultaneously to the protein “Programmed Death-Ligand 1” (PD-L1) and to the vascular endothelial growth factor (VEGF). PD-L1 is a surface protein that acts as a brake on the immune system, a mechanism exploited by cancer cells to protect themselves from attacks by the body’s own defenses. VEGF is a signaling molecule that stimulates the formation of new blood vessels, thereby supplying a tumor with blood, oxygen, and nutrients. The goal of the drug is to activate the body’s immune system against the cancer cells while simultaneously cutting off the tumor’s blood supply. For patients whose tumors are PD-L1-negative, treatment with an immunotherapy agent that targets only one site (PD-1 or PD-L1) (monospecific), in combination with chemotherapy, is not an option. The study investigates whether pumitamig, by simultaneously blocking PD-L1 and VEGF, can serve as an additional treatment option for these patients.

The goal of this Phase 3 study is to investigate whether the additional administration of pumitamig alongside chemotherapy can have a beneficial effect on disease progression compared to chemotherapy with a placebo. To this end, the study will investigate whether it can delay disease progression and prolong patient survival. Patients will be randomly assigned to two parallel groups. In the study arm (Arm 1), patients will receive pumitamig along with chemotherapy; in the control arm (Arm 2), they will receive a placebo along with chemotherapy. The study physicians will select which chemotherapy regimen to use from several standard agents (Nab-paclitaxel or paclitaxel; gemcitabine combined with carboplatin; or eribulin). Both Pumitamig and the placebo are administered as an intravenous infusion. The study is quadruple-blind, meaning that neither the patients nor the individuals involved in the treatment and evaluation know who is receiving Pumitamig and who is receiving the placebo. Treatment will continue as long as the disease does not progress and the treatment is well tolerated. Patients will then be monitored for safety for up to 90 days after the last dose and subsequently followed up regarding their survival—for a total of up to approximately 49 months (about 4 years).

Adult patients aged 18 and older whose breast cancer has recurred locally and is inoperable or has already spread (metastasized) are eligible to participate in the study. Both patients with triple-negative breast cancer and those with a hormone receptor-low, HER2-negative form (hormone receptors only weakly expressed, 1 to 10 percent, and HER2-negative) are eligible. Patients must not have received any prior systemic anticancer therapy for their advanced disease, and the tumor must be PD-L1-negative.