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

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 years and older
• All sexes
• No healthy volunteers
• Adult, Older adult

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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

About this study

Official title: Identification of Predictive Biomarkers of Response to Chemotherapy and Immune Checkpoint Inhibitors in Early Triple Negative Breast Cancer: an Integrative Multiomics Platform

Conditions

Triple Negative Breast Cancer

Being tested

Whole Genome Sequencing, RNA-Sequencing, Microbiome analysis, ctDNA analysis, TCR-β repertoire sequencing

Keywords

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

Medical subject headings

Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Whole Genome SequencingDiagnostic test

  Also called WGS

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

• RNA-SequencingDiagnostic test

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

• Microbiome analysisDiagnostic 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.

• ctDNA analysisDiagnostic test

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

• TCR-β repertoire sequencingDiagnostic test

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

• PBMCs phenotypingDiagnostic test

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

• PembrolizumabDrug

  Pembrolizumab will be given in combination with standard NACT.

• ChemotherapyDrug

  Also called Carboplatin, taxane, anthracycline, cyclophosphamide

  Standard NACT will be given.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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

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

2. 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

   Measured: Up to approximately 60 months

3. Overall survival (OS)

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

   Measured: Up to approximately 60 months

4. 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.

   Measured: After all data are analyzed, up to approximately 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted23 Jun 2023
2. Study start13 Jan 2023
3. Primary completionDec 2026 (estimated)
4. Study completionDec 2029 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.