Идёт набор NCT05916755

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

— Наблюдательное Triple Negative Breast Cancer

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: Whole Genome Sequencing, RNA-Sequencing, Microbiome analysis, ctDNA analysis.
Кому может быть актуально: Состояния в реестре: Triple Negative Breast Cancer. Базовые параметры: от 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Испания
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

Диагностический тест 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.
Диагностический тест RNA-Sequencing
RNA-Sequencing will be performed in tumor tissue from baseline and from residual disease after NACT (if present).
Диагностический тест 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.
Диагностический тест ctDNA analysis
ctDNA analysis will be performed in plasma before and during NACT.
Диагностический тест TCR-β repertoire sequencing
TCR-β repertoire sequencing will be performed in plasma before and during NACT.
Диагностический тест PBMCs phenotyping
PBMCs phenotyping will be performed in plasma before and during NACT.
Препарат Pembrolizumab
Pembrolizumab will be given in combination with standard NACT.
Препарат Chemotherapy
Standard NACT will be given.

Первичные конечные точки

Pathologic complete response (pCR) rate at definitive surgery [Срок оценки: after neoadjuvant treatment and surgery, up to approximately 27-30 weeks]
Event-free survival (EFS) [Срок оценки: Up to approximately 60 months]
Overall survival (OS) [Срок оценки: Up to approximately 60 months]
Identification of biomarkers to predict clinical outcomes (pCR at definitive surgery, EFS, OS). [Срок оценки: After all data are analyzed, up to approximately 60 months]

Критерии участия

Критерии включения

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