Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Immunomodulating Agents

Patients with advanced or metastatic triple negative breast cancer, due to start a new line of systemic therapy (targeted drug or immunotherapy)

Patients undergo a biopsy from a lesion, and give 40ml of blood

Biopsy

Duleek Ranatunga

Elli Tham

Susan Cleator

Peter Hall, MD PhD

Sheeba Irshad, MD PhD

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)

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.

Prospective Evaluation of AI R&D Tool for Patient Stratification - MoA Evaluation in Triple Negative Breast Cancer (PEAR-MET)

Prospective Evaluation of AI R&D Tool for Patient Stratification - Mechanism of Action Evaluation in Triple Negative Breast Cancer (PEAR-MET)

Pseudonymised data will be shared between study sites, such as treatment and outcome data for each patient. No publication will be made revealing individual patient data; only group-level data will be published.

The percentage of patient samples successfully arriving at central lab with \>100k live cells isolated and maintaining 70% cell viability after 4 days in culture with no treatment

The relationship between DNA, RNA and protein levels and patient outcomes

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

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

The performance of Pear image-based biomarkers are established against patients' progression-free survival at 6, 12 and 24 months (evaluated by imaging).

The performance of Pear image-based biomarkers are established against patients' overall survival at 6, 12 and 24 months (evaluated by imaging).

Guys' and St. Thomas Hospital

Barts & The London NHS Trust

Imperial College Healthcare NHS Trust

Nottingham University Hospitals Trust

Hampshire Hospitals NHS Foundation Trust

Ourotech, Inc.

Early TNBC patients receiving neoadjuvant therapy and providing core needle biopsy.

Any approved neoadjuvant therapy can be used based on physician's choice.

Early TNBC patients receiving neoadjuvant therapy and providing core needle biopsy and blood.

Any approved neoadjuvant therapy can be used based on physician's choice.

An additional core needle biopsy is taken to run the Pear Bio test. Test results are not used to inform treatment. Approved neoadjuvant therapy regimens are given to the patient as per standard of care to observe response.

Core needle biopsy

Anjali Sivajothi

Peter Hall

Holly Hogan

Charlotte Wood

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 chemotherapy regimens can be tested simultaneously ex vivo. This study will recruit patients with early TNBC who are planned for standard of care neoadjuvant chemotherapy followed by surgery. The oncologist will be blinded to the response on the Pear Bio tool (the assay will be run in parallel with the patient's neoadjuvant chemotherapy). The primary objective of this study is to establish the sensitivity and specificity of Pear Bio's test against patient outcomes (pathological complete response).

This is a multicenter, UK-based, observational pilot study that aims to determine the accuracy of a new assay, the Pear Bio tool, in predicting pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy for early TNBC. Patients will undergo an additional, mandatory biopsy of the breast tumor before commencing neoadjuvant chemotherapy. The biopsy sample will be run on the Pear Bio tool while the patient receives their standard of care neoadjuvant chemotherapy. As such, for this study, the result from the Pear Bio tool will not be used to inform the choice of neoadjuvant chemotherapy and the treating oncologist will be blinded to the assay results. The pathological outcome from surgery (pCR vs non-pCR) will be collected and used to calculate the specificity of the assay as the primary endpoint of the study. Sensitivity, positive predictive value and negative predictive value will also be measured.

Image-based AI Predictive Biomarkers for Precision Neoadjuvant Triple-negative Breast Cancer Treatment

Prospective Evaluation of Image-based Artificial Intelligence Research and Development Tool for Precision Neoadjuvant Triple-Negative Breast Cancer Treatment

Pseudonymized data will be shared between study sites, such as treatment and outcome data for each patient. No publication will be made revealing individual patient data; only group-level data will be published.

The specificity of Pear image-based biomarkers are established against patient pathological complete response (evaluated on surgical sample post-neoadjuvant therapy).

The sensitivity of Pear image-based biomarkers are established against patient pathological complete response (evaluated on surgical sample post-neoadjuvant therapy).

The positive predictive value of Pear image-based biomarkers are established against patient pathological complete response (evaluated on surgical sample post-neoadjuvant therapy).

The negative predictive value of Pear image-based biomarkers are established against patient pathological complete response (evaluated on surgical sample post-neoadjuvant therapy).

Nervous System Diseases

Rare Diseases

Glioblastoma

Glioma

Brain Neoplasms

Ependymoma

Oligodendroglioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

Patients with a solid primary brain tumor due to undergo surgery as standard of care

Patients undergo a resection from a lesion, and give 40mL of blood

Resection

Waqar Saleem, MRCP FRCR

Matt Williams, FRCR PhD

Pear Bio has developed a 3D microtumor assay and computer vision pipeline through which the response of an individual patient's tumor to different anti-cancer regimens can be tested simultaneously ex vivo. This study will recruit patients with primary brain tumors who are due to undergo surgery.

Oncologists will be blinded to treatment 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 ex vivo model and confirm whether approved therapies exhibit their intended mechanism of action in the model. Secondary objectives include correlating test results to patient outcomes, where available.

This is a multicenter, observational pilot study that aims to determine the feasibility of using the Pear Bio tool in patients with primary solid brain tumors.

Patients who are due to undergo clinically-mandated surgery will provide informed consent to donate excess tissue and a 40mL blood sample.

The samples will be tested on the Pear Bio tool while the patient receives their standard of care treatment. As such, for this study, the result from the Pear Bio tool will not be used to inform the choice of treatment and the treating oncologist will be blinded to the assay results.

The investigators will examine drug mechanism of action (MoA), differentiated response, and correlate that with outcomes seen in the patients treated in routine clinical practice.

Prospective Evaluation of AI R&D Tool in Adult Glioma and Other Primary Brain Tumours (PEAR-GLIO)

The percentage of cultures in which ≥70% of viable tumor cells encapsulated post-isolation on day 0 are still alive on day 3 in the control cultures (no treatment) compared to the number of tumor samples successfully accepted at the study central lab.

The percentage of cultures in which ≥70% of viable immune cells plated post-extraction on day 0 are still alive on day 3 in the control cultures (no treatment) compared to the number of blood samples successfully accepted at the study central lab.

To correlate Pear assay results, biomarkers and outcomes

Categorisation of patients into survival cohorts using the Pear assay

Correlation between biomarkers and clinically relevant outcomes

Measurement of treatment response in the Pear Assay

The correlation between response in the Pear Bio system and PFS in patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Evaluation of AI R&D Tool for Patient Stratification - MoA Evaluation in Triple Negative Breast Cancer (PEAR-MET)	NCT06182306	Breast Cancer Triple Negative...	Biopsy	18 Years -	Ourotech, Inc.
Image-based AI Predictive Biomarkers for Precision Neoadjuvant Triple-negative Breast Cancer Treatment	NCT05435352	Triple Negative... Triple Negative...	Core needle bio...	18 Years -	Ourotech, Inc.
Prospective Evaluation of AI R&D Tool in Adult Glioma and Other Primary Brain Tumours (PEAR-GLIO)	NCT06038760	Brain Tumor Glioma, Maligna... Ependymoma Oligodendroglio... Glioblastoma	Resection	18 Years -	Ourotech, Inc.

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