This phase II trial tests the safety, side effects, and whether dendritic cell-based treatment and pembrolizumab work in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). The term triple-negative breast cancer refers to the fact that the cancer cells don’t have estrogen or progesterone receptors (ER or PR) and also don’t make any or too much of the protein called HER2 (the cells test "negative" on all 3 tests). Dendritic cell-based treatment works by boosting the immune system (a system in our bodies that protects us against infection) to recognize and destroy the cancer cells. Pembrolizumab, is an immune checkpoint inhibitor drug, that works by targeting molecules that act as a check and balance system for immune responses. Immune checkpoint inhibitor drugs are designed to either “unleash” or “enhance” the cancer immune responses that already exist by either blocking inhibitory molecules or by activating stimulatory molecules. Giving dendritic cell-based therapy and pembrolizumab may decrease symptoms and improve quality of life in patients with triple negative breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05539365.
PRIMARY OBJECTIVE:
I. To determine the clinical efficacy and safety and tolerability of a combination of intratumorally injected autologous dendritic cells (DCs) and pembrolizumab in PD-L1 negative treatment-naive and refractory metastatic triple negative breast cancer patients.
SECONDARY OBJECTIVES:
I. To assess progression-free survival and overall survival in metastatic triple negative breast cancer patients that received the combination of intratumorally injected autologous DCs and pembrolizumab.
II. To assess the clinical efficacy in the non-injected target lesion (optional biopsies for this lesion).
EXPLORATORY OBJECTIVES:
I. Comparison (using reverse transcriptase-polymerase chain reaction [RT-PCR], Immunofluorescence [IF] and immunohistochemistry [IHC] on serial sections) of the metastatic tissue specimen with regard to total numbers of infiltrating T cells, their CD4/CD8 ratios, frequencies of FoxP3 cells, and the expression of chemokine receptors on CD4+ and CD8+ T cells (CXCR3, CCR5, CCR4, CCR6, and CXCR4) pre and post treatment.
II. Evaluate the local expression of effector T-cells (Teff)-attracting chemokines (CCR5, CXCL9, CXCL10 and CXCL11) and regulatory T-cells (Treg)-favoring chemokines (CCL22 and CXCL12) using IF and RT-PCR pre and post treatment.
III. Evaluate changes in health-related quality of life (HR-QOL) measures.
OUTLINE:
Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 intratumorally (IT) on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab intravenously (IV) on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and computed tomography (CT) scans at baseline and days 50 and 85.
After completion of study treatment, patients are followed up at 30 and 90 days after the last dose of study drug, and then every 3 months for up to 2 years.
Lead OrganizationRoswell Park Cancer Institute
Principal InvestigatorShipra Gandhi
