Pilot trial of the IL-4 receptor antagonist dupilumab plus pembrolizumab, paclitaxel, and carboplatin in locally advanced triple negative breast cancer (TNBC). Primary 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Dupilumab 600mg subcutaneous initial loading dose, 300mg for subsequent doses; administered every 3 weeks for 4 cycles. Immunotherapy drug FDA approved to treat patients with eczema, asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. Investigational/not yet FDA approved to treat patients with breast cancer.
Pembrolizumab 200mg intravenous every 3 weeks for 4 cycles and one 400mg intravenous dose one week following completion of chemotherapy. Cancer immunotherapy drug FDA approved for the treatment of high-risk, early-stage, triple-negative breast cancer (TNBC).
Paclitaxel 80mg/m2 intravenous weekly for 12 weeks. Chemotherapy FDA-approved for the treatment of patients with breast cancer.
Carboplatin AUC 1.5 intravenous weekly for 12 weeks. Chemotherapy FDA-approved for the treatment of patients with breast cancer.
Mount Sinai Health System
New York, New York, United States
RECRUITINGIncidence of severe immune-related adverse events (irSAE)
Incidence of severe immune-related adverse events within 4 months of therapy. Immune related Severe Adverse Events (irSAE) are defined as: * Any Grade 4 immune-related AE with the exception of hypothyroidism * Any Grade 3 immune-related AE requiring permanent discontinuation of dupilumab and pembrolizumab * Any new Grade 3 or Grade 4 non-hematologic laboratory abnormality, if * medical intervention is required, or * the abnormality leads to hospitalization, or * the abnormality persists for \> 72 hours * Any non-hematologic AE which is considered severe or life-threatening and requires discontinuation of dupilumab and pembrolizumab * Any ≥ Grade 2 immune-mediated uveitis * Any immune-related AE resulting in persistent or significant disability/incapacity (substantial disruption of one's ability to conduct normal life functions) for a period of 30 days or greater * Grade 5 or life-threatening toxicity
Time frame: Within 4 months of therapy
Proportion of patients with pathologic complete response (pCR) with 95 percent Wilson Score interval
Pathologic complete response (pCR) is defined as the lack of invasive cancer in the breast and axilla at time of surgical resection after neoadjuvant therapy. The research team will calculate the proportion of patients with pathologic complete response with 95 percent Wilson Score interval without continuity correction.
Time frame: During procedure, after 13 weeks of neoadjuvant therapy
Proportion of patients with residual cancer burden (RCB) categories 0 and 1 with 95 percent Wilson Score
Residual cancer burden (RCB) categories 0-1 comprise of patients who have achieved pCR (RCB 0) and have minimal tumor burden (RCB 1) after neoadjuvant therapy. The research team will calculate the proportion of patients with residual cancer burden categories 0 and 1 with 95 percent Wilson Score interval without continuity correction.
Time frame: After completion of neoadjuvant therapy (13 weeks)
Proportion of patients who did not experience an invasive breast cancer recurrence (Recurrence-Free Survival (RFS))
Recurrence-free survival (RFS) is measured as the proportion of patients who did not experience an invasive breast cancer recurrence in the ipsilateral breast or regional nodes, distant organ sites, or death from any cause for the specified time period. It is defined as time from start of treatment to occurrence of an invasive breast cancer recurrence in the ipsilateral breast or regional nodes, distant organ sites, or death from any cause. The research team will summarize using Kaplan-Meier method with 95 percent pointwise confidence intervals using complimentary log-log scale. Median RFS with 95 percent confidence interval will be calculated using Brookmeyer and Crowley method. Hazard ratios with 95 percent confidence interval will be estimated using Proportional Hazards Cox regression model.
Time frame: During procedure, after 13 weeks of neoadjuvant therapy
Overall Survival (OS)
Overall survival (OS) is defined as the time from the start of treatment until documented death from any cause. The research team will summarize using Kaplan-Meier method with 95 percent pointwise confidence intervals using complimentary log-log scale. Median RFS with 95 percent confidence interval will be calculated using Brookmeyer and Crowley method. Hazard ratios with 95 percent confidence interval will be estimated using the Cox Proportional Hazards regression model.
Time frame: After completion of neoadjuvant therapy (13 weeks)
Number of immune-related adverse events grades 3-5
Toxicity will be measured by the number immune-related adverse events grades 3-5 and incidence of severe TEAE (Grade 3-5 or serious AEs) according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, as well as based on rates of dose interruptions and drug discontinuations due to adverse events.
Time frame: Within 3 months and 6 months of treatment
Number of adverse events measured using CTCAE Version 5.0
Number of adverse events will be reported according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
Time frame: Within 3 months and 6 months of treatment
Incidence of all-grade immune-related adverse events
Incidence of all-grade immune-related adverse events and severe TEAEs with the combination therapy within 3 months at the last study visit and within 6 months with chart review.
Time frame: Within 3 months and 6 months of treatment
Type of adverse events
The type of severe adverse events will be collected.
Time frame: Within 3 months and 6 months of treatment
Number of dose interruptions
The research team will assess the number of dose interruptions due to AEs with 95 percent Wilson Score interval without continuity correction.
Time frame: Within 3 months and 6 months of treatment
Number of drug discontinuations
The research team will assess the number of drug discontinuations due to AEs with 95 percent Wilson Score interval without continuity correction.
Time frame: Within 3 months and 6 months of treatment
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