Evaluating and Monitoring Immune and Clinical Responses in Early-Stage Triple Negative Breast Cancer Undergoing Neoadjuvant Chemo-immunotherapy With Pembrolizumab

This research study is a prospective, single arm, pilot study, designed to evaluate the correlation between the immune and clinical responses of subjects with untreated Stage II-III triple negative breast cancer (TNBC) undergoing standard of care neoadjuvant chemo- immunotherapy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Stage II; Breast Cancer Stage III; Breast Cancer Invasive; Breast Cancer Triple Negative

Detailed Description

Primary Objective:

I. To determine whether standard of care neoadjuvant chemo-immunotherapy leads to the induction of a pro-inflammatory cytokine milieu (characterized by high IFN- γ, IFN-α, IL-6 and low TGF-β) in the blood which is induced within 24 hours of treatment initiation, persists through the course of the therapy and is associated with pathologic complete response in the tissue.

Secondary Objectives:

I. To determine whether the spatially resolved tissue TGF-β induced transcriptomic signatures or lack of innate interferon inducible genes/effector CD8 modules are abundant in tumors from TNBC patients that do not show pathologic complete response in the tissue at the end of standard of care neoadjuvant chemo- immunotherapy.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Ruth Sacks, MD; Phone Number: 404-778-1900; Email: rlsacks@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University/Winship Cancer Institute
      • Principal Investigator: Ruth Sacks, MD
      • Contact: Nina Kimball; Phone Number: 404-778-8145; Email: ndobbs@emory.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All patients enrolled to the study who started at least one-dose of standard of care neoadjuvant chemo-immunotherapy with blood samples available for pre- and <=24 hour post-infusion at first cycle.

Description

Inclusion Criteria:

• Newly diagnosed, previously untreated, non-metastatic Stage II-III invasive breast cancer
• Estrogen receptor IHC expression ≤10%; progesterone receptor IHC expression ≤ 10%; HER2 negative
• HER2 negativity is defined as either of the following by local laboratory assessment:
• IHC 0, 1+, or 2+ and In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 <2.0 or single probe average HER2 gene copy number <4 signals/cell)
• No prior chemotherapy, endocrine therapy, or immunotherapy
• Willingness and ability of the subject to comply with scheduled visits, standard of care drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.
• Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
• Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs.
• Patients on steroid medications (i.e. prednisone, dexamethasone, etc.) that are not part of the standard pre-medications and/or take home medications that are included as a part of medication regimen for the pre-operative chemo-immunotherapy described in the study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study.
• 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.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with study agents. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the cytokine milieu in the blood	The change in the cytokine milieu specifically IFN-γ, IFN-α, IL-6 and TGF-β in the blood during standard of care neoadjuvant chemo-immunotherapy and its association with pathologic complete response in the tissue	From baseline within 24 hours of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the transcriptomic signatures in the tissue	The transcriptomic signatures of TGF-β induced genes and innate interferon inducible genes/effector CD8 in the tissue specimens collected at baseline (archival tissue obtained prior to standard of care neoadjuvant chemo- immunotherapy) and after completion of treatment at the time of surgery.	From baseline within 24 hours of surgery

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ruth Sacks, MD, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Estimated): April 10, 2024
• Study Completion (Estimated): April 10, 2025

Study Registration Dates

• First Submitted: May 18, 2023
• First Submitted That Met QC Criteria: May 18, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: STUDY00005452 (Other Identifier: Emory University Hospital/Winship Cancer Institute); P30CA138292 (U.S. NIH Grant/Contract); NCI-2023-02943 (Registry Identifier: Registry ID: CTRP (Clinical Trial Reporting Program)]); WINSHIP5818-22 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No