Clinical trial NCT05877859: Evaluating and Monitoring Immune and Clinical Responses in Early-Stage Triple Negative Breast Cancer Undergoing Neoadjuvant Chemo-immunotherapy With Pembrolizumab
Official title: Evaluating and Monitoring Immune and Clinical Responses in Early-Stage Triple Negative Breast Cancer Undergoing Neoadjuvant Chemo-immunotherapy With Pembrolizumab
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer Triple Negative
Breast Cancer Stage II
Breast Cancer Stage III
Breast Cancer Invasive
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2023-05-26
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in the cytokine milieu in the blood
timeFrame: From baseline within 24 hours of surgery
Secondary outcomes:
measure: Change in the transcriptomic signatures in the tissue
timeFrame: From baseline within 24 hours of surgery
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University Hospital/Winship Cancer Institute
name: Ruth Sacks, MD
role: PRINCIPAL_INVESTIGATOR
References: