Neoadjuvant Dupilumab, Pembrolizumab, Paclitaxel, and Carboplatin in Locally Advanced Triple Negative Breast Cancer

NCT06637306 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: PRMC-24-125
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Locally Advanced Triple Negative Breast Cancer; TNBC - Triple-Negative Breast Cancer

Keywords

Dupilumab; Pembrolizumab; IL-4 Receptor Antagonist; Breast Cancer; Triple Negative; Locally Advanced

Outcome Measures

Primary Outcomes (1)

• Incidence 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

  Within 4 months of therapy

Secondary Outcomes (10)

• 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

Study Arms (1)

Patients with locally advanced TNBC

EXPERIMENTAL

Patients with advanced triple negative breast cancer (TNBC).

Drug: Dupilumab; Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Dupilumab DRUG

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.

Also known as: DUPIXENT

Patients with locally advanced TNBC

Pembrolizumab DRUG

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).

Also known as: KEYTRUDA

Patients with locally advanced TNBC

Paclitaxel DRUG

Paclitaxel 80mg/m2 intravenous weekly for 12 weeks. Chemotherapy FDA-approved for the treatment of patients with breast cancer.

Also known as: TAXOL

Patients with locally advanced TNBC

Carboplatin DRUG

Carboplatin AUC 1.5 intravenous weekly for 12 weeks. Chemotherapy FDA-approved for the treatment of patients with breast cancer.

Patients with locally advanced TNBC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
• Receipt of a live vaccine within 30 days of planned start of study medication.
• History of irAE in response to prior immunotherapy that has not improved to a Grade 0 or 1; this does not include chronic conditions such as endocrinopathies which can be treated with hormone replacement therapy.
• History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis attributed to prior use of cancer immunotherapy that required immune-suppressive doses of glucocorticoids to assist with management. History of radiation pneumonitis treated with glucocorticoids.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Rima Patel: lead

Study Sites (1)

Mount Sinai Health System

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

dupilumab; pembrolizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Rima Patel, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Joseph Sparano, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rima Patel, MD

CONTACT

(212) 604-6010; Rima.Patel2@mssm.edu

Katherine Vandris

CONTACT

Katherine.Vandris@mssm.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Open Label, Single Arm Trial.

Study Record Dates

• First Submitted: October 9, 2024
• First Posted: October 15, 2024
• Study Start: March 5, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose. For individual participant data meta-analysis. Contact the Sponsor-Investigator via email: Rima.Patel2@mssm.edu

Locations

US (1)