Pilot Trial of the IL-4 Receptor Antagonist Dupilumab Plus Pembrolizumab, Paclitaxel, and Carboplatin in Locally Advanced Triple Negative Breast Cancer
Objective: To assess the safety of neoadjuvant dupilumab and pembrolizumab plus weekly paclitaxel and carboplatin as measured by the proportion of severe immune-related adverse events (irAEs) in patients with locally advanced TNBC. Secondary
Objectives: To determine the rates of pathologic complete response with the addition of dupilumab to NAC and pembrolizumab; to determine the rate of residual cancer burden 0-1; to estimate the recurrence-free survival and overall survival; to assess the toxicity of the combination of dupilumab, pembrolizumab, and paclitaxel-carboplatin.
• Patients with pathologically confirmed diagnosis of triple negative breast cancer, as defined by the most recent ASCO/CAP guidelines.
• Patients must have previously untreated, localized TNBC with either tumor size ≥ 2 centimeters (T2-4N0) or lymph node involvement with at least a 1cm tumor (T1c-T4N1-3).
• Patients must have previously untreated disease with no prior definitive breast surgery, radiation therapy, or systemic chemotherapy with therapeutic intent for this breast cancer.
• Patients must be eligible to receive chemotherapy agents in the study including paclitaxel and carboplatin.
• Patients must be willing and able to provide blood samples at the time points indicated in the study calendar.
• Patients must be willing and able to have core needle biopsies of tumor prior to initiation of treatment. Should patients undergo pre-treatment or on-treatment biopsy procedure and inadequate number of biopsies are obtained, they may proceed with initiation/continuation of treatment at the discretion of the investigator and treating physician.
• Age ≥ 18 years.
• ECOG performance status 0-1.
• Adequate organ and marrow function as defined below:
‣ absolute neutrophil count ≥ 1,500/mcL
⁃ platelets ≥ 100,000/mcl
⁃ total bilirubin within normal institutional limits
⁃ AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
⁃ creatinine within normal institutional limits
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
∙ A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.