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

NCT ID: NCT05916755

Last Updated: 2023-06-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-01-13

Study Completion Date

2029-12-31

Brief Summary

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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.

Detailed Description

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The combination of pembrolizumab, an immune checkpoint inhibitor (ICI), with neoadjuvant chemotherapy (NACT) increases pathologic complete response (pCR) and event-free survival (EFS) in patients with early triple negative breast cancer (eTNBC). However, not all patients equally benefit from a treatment that may have relevant adverse events (AEs).

Objectives: (1) To establish predictive biomarkers of response to NACT + ICI in eTNBC by correlating data coming from different layers of omics performed in different tissues, together with imaging, with pCR, EFS, and overall survival (OS). (2) To integrate data generated from (1), and clinical data, and explore multivariate predictive models of response to NACT + ICI.

Methods: Patients with stage II-III TNBC candidates to receive NACT +/- ICI will be included. Collected samples and type of analysis: (1) Tumor tissue (baseline and from residual disease after NACT): whole genome sequencing (WGS) and RNA-Seq will be performed (Hartwig sequencing platform and analytical pipeline), tissue immune phenotyping (PD-L1, T and B infiltrating lymphocytes, among others), and microbiome analysis (16S rRNA); (2) Blood (before and during NACT): circulating tumor DNA (ctDNA) analysis (targeted gene panel and shallow WGS), T-cell receptor beta (TCR-β) repertoire sequencing and analysis (ImmunoSeq hsTCRβ kit and immunoSEQ), and peripheral blood mononuclear cells (PBMCs) phenotyping; (3) Stools and saliva (before and during NACT): microbiome analysis (16S rRNA); (4) Breast MRI imaging (before and after NACT): radiomics analysis. 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. The aim is to provide more personalized treatment efficacy and risk for relapse estimates.

Expected outcome: To develop a clinical tool to assist clinicians in the process of treatment decision-making in eTNBC, in order to maximize patient's benefit and quality of life, while minimizing AEs and financial burden to the health system.

Conditions

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Triple Negative Breast Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort A

Pembrolizumab + neoadjuvant chemotherapy

Whole Genome Sequencing

Intervention Type DIAGNOSTIC_TEST

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

RNA-Sequencing

Intervention Type DIAGNOSTIC_TEST

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

Microbiome analysis

Intervention Type 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.

ctDNA analysis

Intervention Type DIAGNOSTIC_TEST

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

TCR-β repertoire sequencing

Intervention Type DIAGNOSTIC_TEST

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

PBMCs phenotyping

Intervention Type DIAGNOSTIC_TEST

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

Pembrolizumab

Intervention Type DRUG

Pembrolizumab will be given in combination with standard NACT.

Chemotherapy

Intervention Type DRUG

Standard NACT will be given.

Cohort B

Neoadjuvant chemotherapy

Whole Genome Sequencing

Intervention Type DIAGNOSTIC_TEST

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

RNA-Sequencing

Intervention Type DIAGNOSTIC_TEST

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

Microbiome analysis

Intervention Type 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.

ctDNA analysis

Intervention Type DIAGNOSTIC_TEST

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

TCR-β repertoire sequencing

Intervention Type DIAGNOSTIC_TEST

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

PBMCs phenotyping

Intervention Type DIAGNOSTIC_TEST

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

Chemotherapy

Intervention Type DRUG

Standard NACT will be given.

Interventions

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Whole Genome Sequencing

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

Intervention Type DIAGNOSTIC_TEST

RNA-Sequencing

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

Intervention Type DIAGNOSTIC_TEST

Microbiome analysis

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.

Intervention Type DIAGNOSTIC_TEST

ctDNA analysis

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

Intervention Type DIAGNOSTIC_TEST

TCR-β repertoire sequencing

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

Intervention Type DIAGNOSTIC_TEST

PBMCs phenotyping

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

Intervention Type DIAGNOSTIC_TEST

Pembrolizumab

Pembrolizumab will be given in combination with standard NACT.

Intervention Type DRUG

Chemotherapy

Standard NACT will be given.

Intervention Type DRUG

Other Intervention Names

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WGS Carboplatin, taxane, anthracycline, cyclophosphamide

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* Metastatic disease on imaging (stage 4)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vall d'Hebron Institute of Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Vall d'Hebron Institute of Oncology

Barcelona, , Spain

Site Status RECRUITING

Countries

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Spain

Facility Contacts

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Mafalda Oliveira, MD PhD

Role: primary

+34932543450

Other Identifiers

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PR(AG)165-2021

Identifier Type: -

Identifier Source: org_study_id

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