This phase I trial tests the safety and side effects of adding dupilumab to pembrolizumab, paclitaxel and carboplatin and how well they work in treating patients with triple negative breast cancer (TNBC) that has spread to nearby tissues or lymph nodes (locally advanced). Dupilumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Adding dupilumab to pembrolizumab, paclitaxel and carboplatin may be safe, tolerable and/or effective in treating patients with locally advanced TNBC.
Additional locations may be listed on ClinicalTrials.gov for NCT06637306.
Locations matching your search criteria
United States
New York
New York
Icahn School of Medicine at Mount SinaiStatus: Active
Contact: Rima Patel
Phone: 212-241-3175
PRIMARY OBJECTIVE:
I. To assess the safety of neoadjuvant dupilumab and pembrolizumab plus weekly paclitaxel and carboplatin in patients with locally advanced TNBC.
SECONDARY OBJECTIVES:
I. To determine the rates of pathologic complete response (pCR) with the addition of dupilumab to neoadjuvant chemotherapy (NAC) and pembrolizumab.
II. To determine the rate of residual cancer burden 0-1 with the addition of dupilumab to neoadjuvant pembrolizumab and chemotherapy.
III. To estimate the recurrence-free survival.
IV. To estimate the overall survival.
V. To further assess the toxicity of the combination of dupilumab, pembrolizumab, and paclitaxel-carboplatin.
EXPLORATORY OBJECTIVES:
I. To determine the effects of dupilumab on T-helper-2 (TH2) and T-helper-1 (TH1) signatures in the tumor microenvironment and associate them with response and adverse events.
II. To assess changes in the tumor immune microenvironment with the addition of dupilumab and associate them with response and adverse events.
III. To determine whether the addition of dupilumab induces changes in peripheral blood mononuclear cells and whether these changes are associated with response and adverse events.
IV. To assess the impact of dupilumab on the systemic immune milieu and its association with response and adverse events.
V. To determine whether the addition of dupilumab causes changes in circulating tumor-derived deoxyribonucleic acid (ctDNA) and whether these changes are associated with response and adverse events.
OUTLINE:
NEOADJUVANT THERAPY: Patients receive dupilumab subcutaneously (SC) on day 1 of cycles 1-4, pembrolizumab intravenously (IV) over 30 minutes on day 1 of cycles 1-5, carboplatin IV over 15-60 minutes on days 1, 8, and 15 on of cycles 1-4, and paclitaxel IV over at least 1 hour on days 1, 8, and 15 of cycles 1-4. Cycles repeat every 21 days for up to 13 weeks in the absence of disease progression or unacceptable toxicity.
DEFINITIVE SURGERY: After completion of neoadjuvant treatment, patients undergo definitive surgery per standard of care. Patients may also undergo radiation therapy as indicated per standard of care.
ADJUVANT THERAPY: Starting at least 6 weeks after completion of neoadjuvant therapy, patients receive pembrolizumab on day 1of each cycle per standard of care. Cycles repeat every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients with residual disease also receive adjuvant doxorubicin and cyclophosphamide once every 3 weeks (Q3W) for up to 4 cycles concurrently with pembrolizumab per standard of care.
Additionally, patients undergo core needle biopsy at baseline and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 3 weeks following neoadjuvant therapy, 3 weeks after definitive surgery, every 3 months during adjuvant pembrolizumab therapy, then every 6 months for up to 5 years.
Lead OrganizationIcahn School of Medicine at Mount Sinai
Principal InvestigatorRima Patel
