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

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

NCT ID: NCT05916755

Condition: Triple Negative Breast Cancer

Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Cyclophosphamide
Carboplatin
Pembrolizumab

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

Study type: Observational

Overall status: Recruiting

Study design:

Time perspective: Prospective

Intervention:

Intervention type: Diagnostic Test
Intervention name: Whole Genome Sequencing
Description: Whole genome sequencing (WGS) will be performed in tumor tissue from baseline and from residual disease after neoadjuvant chemotherapy (NACT), if present.
Arm group label: Cohort A
Arm group label: Cohort B

Other name: WGS

Intervention type: Diagnostic Test
Intervention name: RNA-Sequencing
Description: RNA-Sequencing will be performed in tumor tissue from baseline and from residual disease after NACT (if present).
Arm group label: Cohort A
Arm group label: Cohort B

Intervention type: Diagnostic Test
Intervention name: Microbiome analysis
Description: 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.
Arm group label: Cohort A
Arm group label: Cohort B

Intervention type: Diagnostic Test
Intervention name: ctDNA analysis
Description: ctDNA analysis will be performed in plasma before and during NACT.
Arm group label: Cohort A
Arm group label: Cohort B

Intervention type: Diagnostic Test
Intervention name: TCR-β repertoire sequencing
Description: TCR-β repertoire sequencing will be performed in plasma before and during NACT.
Arm group label: Cohort A
Arm group label: Cohort B

Intervention type: Diagnostic Test
Intervention name: PBMCs phenotyping
Description: PBMCs phenotyping will be performed in plasma before and during NACT.
Arm group label: Cohort A
Arm group label: Cohort B

Intervention type: Drug
Intervention name: Pembrolizumab
Description: Pembrolizumab will be given in combination with standard NACT.
Arm group label: Cohort A

Intervention type: Drug
Intervention name: Chemotherapy
Description: Standard NACT will be given.
Arm group label: Cohort A
Arm group label: Cohort B

Other name: Carboplatin, taxane, anthracycline, cyclophosphamide

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.

Detailed description: 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.

Criteria for eligibility:

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

Sampling method: Non-Probability Sample
Criteria:
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)

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Vall d'Hebron Institute of Oncology

Address:
City: Barcelona
Zip: 08035
Country: Spain

Status: Recruiting

Contact:
Last name: Mafalda Oliveira, MD PhD

Phone: +34932543450
Email: moliveira@vhio.net

Start date: January 13, 2023

Completion date: December 2029

Lead sponsor:
Agency: Vall d'Hebron Institute of Oncology
Agency class: Other

Source: Vall d'Hebron Institute of Oncology

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05916755