Predictive Biomarkers of Response to Checkpoint Inhibitors in Triple Negative Breast Cancer: a Multiomics Platform

NCT05916755 | Recruiting FDA Drug

• 1 other identifier: PR(AG)165-2021
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with stage II-III Triple negative breast cancer (TNBC) candidates to receive neoadjuvant chemotherapy (NACT) +/- immune checkpoint inhibitor (ICI) will be included. Several samples from different tissues will be analyzed through different omics to establish predictive biomarkers of response to the treatment. Multiple algorithms will then be used to look for an integrative predictive algorithm that incorporates multi-parameter inputs in order to develop a clinical tool to assist clinicians in the process of treatment decision-making in TNBC.

Conditions

Triple Negative Breast Cancer

Keywords

Circulating biomarkers; clinical tool; immune checkpoint inhibitors; integrative algorithm; microbiome; multiomics; neoadjuvant chemotherapy; predictive biomarkers; radiomics; RNA-Sequencing; triple negative breast cancer; WGS

Outcome Measures

Primary Outcomes (4)

• Pathologic complete response (pCR) rate at definitive surgery

  The rate (given as a percentage) of patients with a pCR at definitive surgery using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) from the American Joint Committee on Cancer (AJCC) staging criteria

  after neoadjuvant treatment and surgery, up to approximately 27-30 weeks

• Event-free survival (EFS)

  EFS is defined as the time from the start of neoadjuvant treatment to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause

  Up to approximately 60 months

• Overall survival (OS)

  OS is defined as the time from starting neoadjuvant treatment until death due to any cause

  Up to approximately 60 months

• Identification of biomarkers to predict clinical outcomes (pCR at definitive surgery, EFS, OS).

  The clinical data (pCR at definitive surgery, EFS, OS) will be integrated with the results from the multiomics platform and multivariate predictive models of response to neoadjuvant chemotherapy (NACT) + immune checkpoint inhibitor (ICI) will be explored. Precisely, the multiomics platform will analyze: 1. RNA-Sequencing of the initial tumor and residual disease (if present) 2. microbiome analysis of the saliva and feces, 3. circulating tumor DNA (ctDNA) analysis (targeted gene panel and shallow WGS), 4. Tissue immune phenotyping, 5. T-cell receptor beta (TCR-β) repertoire sequencing and analysis using ImmunoSeq hsTCRβ kit and immunoSEQ, 6. Breast MRI imaging (before and after NACT), Multiple algorithms including Multiple Kernel Learning, Multi-Omics Factor Analysis (MOFA) and Method for the Functional Integration of Spatial and Temporal Omics data (MEFISTO) will then be used to look for an integrative predictive algorithm that incorporates multi-parameter inputs.

  After all data are analyzed, up to approximately 60 months

Study Arms (2)

Cohort A

Pembrolizumab + neoadjuvant chemotherapy

Diagnostic Test: Whole Genome Sequencing; Diagnostic Test: RNA-Sequencing; Diagnostic Test: Microbiome analysis; Diagnostic Test: ctDNA analysis; Diagnostic Test: TCR-β repertoire sequencing; Diagnostic Test: PBMCs phenotyping; Drug: Pembrolizumab; Drug: Chemotherapy

Cohort B

Neoadjuvant chemotherapy

Diagnostic Test: Whole Genome Sequencing; Diagnostic Test: RNA-Sequencing; Diagnostic Test: Microbiome analysis; Diagnostic Test: ctDNA analysis; Diagnostic Test: TCR-β repertoire sequencing; Diagnostic Test: PBMCs phenotyping; Drug: Chemotherapy

Interventions

Whole Genome Sequencing DIAGNOSTIC_TEST

Whole genome sequencing (WGS) will be performed in tumor tissue from baseline and from residual disease after neoadjuvant chemotherapy (NACT), if present.

Also known as: WGS

Cohort A; Cohort B

RNA-Sequencing DIAGNOSTIC_TEST

RNA-Sequencing will be performed in tumor tissue from baseline and from residual disease after NACT (if present).

Cohort A; Cohort B

Microbiome analysis DIAGNOSTIC_TEST

Microbiome analysis will be performed in stools and saliva before, during NACT and at the end of adjuvant systemic therapy if adjuvant systemic therapy is clinically indicated.

Cohort A; Cohort B

ctDNA analysis DIAGNOSTIC_TEST

ctDNA analysis will be performed in plasma before and during NACT.

Cohort A; Cohort B

TCR-β repertoire sequencing DIAGNOSTIC_TEST

TCR-β repertoire sequencing will be performed in plasma before and during NACT.

Cohort A; Cohort B

PBMCs phenotyping DIAGNOSTIC_TEST

PBMCs phenotyping will be performed in plasma before and during NACT.

Cohort A; Cohort B

Pembrolizumab DRUG

Pembrolizumab will be given in combination with standard NACT.

Cohort A

Chemotherapy DRUG

Standard NACT will be given.

Also known as: Carboplatin, taxane, anthracycline, cyclophosphamide

Cohort A; Cohort B

Eligibility Criteria

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

Study Population

Patients with stage II-III TNBC candidates to receive NACT +/- ICI will be included

You may qualify if:

• Histologically documented TNBC (negative human epidermal growth factor receptor 2 \[HER2\], estrogen receptor \[ER\], and progesterone receptor \[PgR\] status)
• Stage 2 - 3 defined by the American Joint Committee of Cancer (AJCC) staging criteria 8th edition for breast cancer as assessed by the investigator based on radiological and/or clinical assessment
• Patient is a candidate to receive NACT with or without ICI as assessed by the investigator
• Patient is ≥ 18 years old at the time of consent to participate in this trial

You may not qualify if:

• Metastatic disease on imaging (stage 4)

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead

Study Sites (1)

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue, Blood samples, Stool, Saliva

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Base Sequence; pembrolizumab; Drug Therapy; Carboplatin; taxane; Anthracyclines; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Therapeutics; Coordination Complexes; Organic Chemicals; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2023
• First Posted: June 23, 2023
• Study Start: January 13, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 23, 2023

Record last verified: 2023-06

Locations

ES (1)