Pilot Trial of the IL-4 Receptor Antagonist Dupilumab Plus Pembrolizumab, Paclitaxel, and Carboplatin in Locally Advanced Triple Negative Breast Cancer
Overview
- Phase
- Early Phase 1
- Intervention
- Paclitaxel
- Conditions
- Locally Advanced Triple Negative Breast Cancer
- Sponsor
- Rima Patel
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Incidence of severe immune-related adverse events (irSAE)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Rima Patel
Assistant Professor
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- •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-
- •Adequate organ and marrow function as defined below:
- •absolute neutrophil count ≥ 1,500/mcL
Exclusion Criteria
- •Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or any treatment with therapeutic intent for the breast cancer.
- •Patients may not be receiving any other investigational agents.
- •Patients who have any distant metastases and considered to have Stage IV disease.
- •Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
- •Patients with active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable.
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, dupilumab or pembrolizumab used in study. Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps).
- •HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with \<350 CD4+ T cells/microliter in the peripheral blood.
- •Known active Hepatitis B (e.g., HBV detected by PCR or active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
- •Known, untreated helminth infections. Patients with prior history of a helminth infection who were fully treated are permitted.
Arms & Interventions
Patients with locally advanced TNBC
Patients with advanced triple negative breast cancer (TNBC).
Intervention: Paclitaxel
Patients with locally advanced TNBC
Patients with advanced triple negative breast cancer (TNBC).
Intervention: Carboplatin
Patients with locally advanced TNBC
Patients with advanced triple negative breast cancer (TNBC).
Intervention: Dupilumab
Patients with locally advanced TNBC
Patients with advanced triple negative breast cancer (TNBC).
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Incidence of severe immune-related adverse events (irSAE)
Time Frame: Within 4 months of therapy
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
Secondary Outcomes
- Number of adverse events measured using CTCAE Version 5.0(Within 3 months and 6 months of treatment)
- Proportion of patients with pathologic complete response (pCR) with 95 percent Wilson Score interval(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(After completion of neoadjuvant therapy (13 weeks))
- Proportion of patients who did not experience an invasive breast cancer recurrence (Recurrence-Free Survival (RFS))(During procedure, after 13 weeks of neoadjuvant therapy)
- Overall Survival (OS)(After completion of neoadjuvant therapy (13 weeks))
- Number of immune-related adverse events grades 3-5(Within 3 months and 6 months of treatment)
- Incidence of all-grade immune-related adverse events(Within 3 months and 6 months of treatment)
- Type of adverse events(Within 3 months and 6 months of treatment)
- Number of dose interruptions(Within 3 months and 6 months of treatment)
- Number of drug discontinuations(Within 3 months and 6 months of treatment)