Prospective Evaluation of AI R&D Tool for Patient Stratification - MoA Evaluation in Triple Negative Breast Cancer (PEAR-MET)
- Conditions
- Breast CancerTriple Negative Breast Cancer
- Interventions
- Procedure: Biopsy
- Registration Number
- NCT06182306
- Lead Sponsor
- Ourotech, Inc.
- Brief Summary
Pear Bio has developed an organ-on-a-chip device together with a computer vision pipeline through which the response of an individual patient's tumor to different systemic therapy regimens can be tested simultaneously ex vivo. This study will recruit patients with advanced or metastatic triple negative breast cancer who are due to start a clinically-indicated new line of therapy.
The oncologist will be blinded to the response on the Pear Bio tool (the assay will be run in parallel with the patient's treatment). The primary objective of this study is to establish the sensitivity and specificity of Pear Bio's test against patient outcomes (response, progression-free survival, overall survival)
- Detailed Description
This is a UK-based observational study that aims to discover novel predictive biomarkers with the potential to guide treatment decision making and prolong PFS and OS in patients with advanced TNBC. Patients will undergo a mandatory, study-specific core needle biopsy or fine needle aspiration of the breast tumour or metastasis before commencing their next line of therapy. The research sample will be run on Pear Bio's test whilst the patient receives therapy as per their physician's choice. This study will not use Pear Bio's tool to inform the choice of treatment, with the treating oncologist being blinded to the test results. Treatment response data will be collected at multiple timepoints to conduct analyses on the study's secondary and tertiary objectives.
Fresh tissue resections that arrive at Pear Bio's lab will undergo processing, cell culture and various drug dosing and omics assays (depending on extracted cell numbers). Tumour samples will be processed using a cell isolation kit to retrieve a viable single-cell suspension. A minimum of 100,000 cells (10,000 viable cells per chip) will be used for staining with live and dead cell-tracking dyes. In parallel, blood vials will be processed for PBMCs and further effector cell extraction (flow cytometry, Dynabeads, etc). The remaining cells will be used for sequencing (DNA/RNA), fixed for immunofluorescence characterisation of biomarkers/receptor status or used for further omics assays (if cell numbers allow). This may include tumour mutational burden and microsatellite instability testing.
The stained cells will be cultured in a biomimetic hydrogel within Pear Bio's organ-on-a-chip to provide a physiological 3D environment for drug dosing experiments. Using a microfluidic device, samples in each chip will be exposed to approved therapies (either as monotherapy or combination therapies, as outlined below) over multiple days.
In parallel, PBMCs will be extracted from whole blood, characterised and sorted via flow cytometry and fluorescence-activated cell sorting (FACS) or magnetic beads selection. Cells of interest (e.g. CD8+ T cells) will be used for culture in Pear Bio's chips jointly with cells isolated from the matched tumour sample. To test immunotherapies, tumour cells will be co-cultured with immune cells in a modified organ-on-a-chip architecture. Chips receiving immunotherapies may be tested for tumour mutational burden and/or microsatellite instability.
Confocal microscopy will be conducted daily to collect 3D image data of the cells and track their position and behaviour over time. At the end of the assay, the 3D cell cultures will be fixed for further 3D immunofluorescence analyses or used for embedding, sectioning and assessment of spatial transcriptomics. For targeted therapies, RNAseq, IF and other omics data will be integrated to confirm drug MoA and identify other potential therapeutic targets. Concurrently, 3D image data is processed through a computer vision pipeline to measure functional metrics of the ex vivo 3D cell cultures, including cell viability, cell culture width and cell migration, both at a bulk tumour level and at a single-cell resolution. For immunotherapies, additional metrics such as immune cell infiltration and immune cell killing will be recorded. A patient report is then generated to outline an individual patient sample's response to each therapy tested.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Trial Cohort Biopsy Patients with advanced or metastatic triple negative breast cancer, due to start a new line of systemic therapy (targeted drug or immunotherapy)
- Primary Outcome Measures
Name Time Method Establish a functional dose of each commonly used FDA approved therapeutic/combination 6 months To conduct dose-response analysis for each commonly used FDA approved therapy, or combination of therapies, to establish the correct dose in the Pear Bio system
- Secondary Outcome Measures
Name Time Method OS prediction accuracy 2 years The performance of Pear image-based biomarkers are established against patients' overall survival at 6, 12 and 24 months (evaluated by imaging).
ORR prediction accuracy 3 months The performance (sensitivity, specificity, PPV and NPV) of Pear image-based biomarkers are established against patients' overall response rate (ORR) as defined by RECIST 1.1 guidelines
PFS prediction accuracy 12-24 months The performance of Pear image-based biomarkers are established against patients' progression-free survival at 6, 12 and 24 months (evaluated by imaging).
Trial Locations
- Locations (3)
Barts Hospital NHS Trust
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Guys and St. Thomas Hospital NHS Trust
🇬🇧London, United Kingdom