Prospective Evaluation of AI R&D Tool for Patient Stratification: a Trial for Renal Immuno-oncology Model Experimental Evaluation 2 (PEAR-TREE2)

Pear Bio has developed a predictive biomarker technology that combines 3D cell culture, microscopy and computer vision to measure the response of an individual patient's tumor sample to different systemic therapy regimens that are tested simultaneously ex vivo.

This study will recruit patients with advanced or metastatic kidney 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 test (the test 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 results against patient outcomes (objective response, progression-free survival, depth and duration of response, overall survival).

Study Overview

• Status: Terminated
• Conditions: Kidney Cancer; Renal Cell Cancer Metastatic
• Intervention / Treatment: Procedure: Biopsy

Detailed Description

This is a multicenter, international, observational pilot study that aims to determine the accuracy of a new assay, the Pear Bio test, in predicting response rate (ORR) in patients receiving standard of care systemic therapies for kidney cancer. Patients will undergo an additional, mandatory core needle biopsy of a lesion before commencing their next line of therapy. 40mL of blood will also be collected from each patient.

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

The investigators will measure objective response rate (ORR) and other outcome metrics (PFS, DoR, OS, etc.). The Pear Bio test results will be compared to the actual patient outcomes to determine the test's sensitivity, specificity, positive predictive value and negative predictive value.

• Study Type: Observational
• Enrollment (Actual): 7

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W6 8RF
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, HA6 2RN
    • Mount Vernon Cancer Centre
  • London, United Kingdom
    • Royal Free NHS Foundation Trust
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Addenbrooke's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with advanced or metastatic kidney cancer, due to start a new line of therapy

Description

Inclusion:

1. Able to give written informed consent prior to admission to this study.
2. Female or male aged ≥18 years.

3. Evidence of advanced RCC with intention to receive systemic therapy, defined as:

   • Clinical suspicion of advanced RCC with intention to undergo a clinically-mandated biopsy and subsequent systemic therapy OR
   • Histological evidence of advanced RCC with intention to undergo subsequent systemic therapy and willing to undergo additional research biopsy
4. At least one lesion evaluable under RECIST 1.1 criteria
5. Willing to donate at least two additional core biopsy samples prior to starting subsequent systemic therapy.
6. Willing to undergo venous sampling for 40mL of blood

Exclusion:

1. Early stage kidney cancer
2. Patients who do not have kidney cancer
3. Patients with RCC that do not intend to receive systemic therapy
4. Patients who have already commenced systemic therapy with no plans of changing the systemic therapy after the collection of the core needle biopsy.
5. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
6. Previous diagnosis of other cancer. Previously treated cancer may be acceptable in some circumstances (e.g. surgery for an unrelated cancer > 5 years ago) after discussion with the Sponsor.
7. No lesions are amenable to biopsy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Trial Cohort; Patients with advanced or metastatic kidney cancer, due to start a new line of systemic therapy (targeted drug, immunotherapy, etc.)	Procedure: Biopsy; Patients undergo a biopsy from a lesion, and give 40ml of blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate correlation accuracy (sensitivity & specificity)	The sensitivity, specificity PPV and NPV of Pear image-based biomarkers are established against patient ORR (evaluated on imaging).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response rate correlation accuracy (sensitivity & specificity)	The sensitivity, specificity PPV and NPV of Pear image-based biomarkers are established against patients achieving a complete response (evaluated by imaging).	2 years
Deep Response rate correlation accuracy (sensitivity & specificity)	The sensitivity, specificity PPV and NPV of Pear image-based biomarkers are established against patients achieving a deep response (evaluated by imaging).	2 years
Durable Response rate correlation accuracy (sensitivity & specificity)	The sensitivity, specificity PPV and NPV of Pear image-based biomarkers are established against patients achieving a durable response at 6, 12 and 24 months (evaluated by imaging).	2 years
PFS prediction accuracy	The performance of Pear image-based biomarkers are established against patients progression-free survival at 6, 12 and 24 months (evaluated by imaging).	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Culture success rate	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	4 days
Hazard ratio by biomarker group	The hazard ratio for PFS and OS between Pear-assay biomarker-high and biomarker-low groups	2 years
OS prediction accuracy	The performance of Pear image-based biomarkers are established against patients overall survival.	2 years

Collaborators and Investigators

• Sponsor: Ourotech, Inc.
• Collaborators: Royal Free Hospital NHS Foundation Trust; Imperial College Healthcare NHS Trust; Cambridge University Hospitals NHS Trust; East & North Herts NHS Trust
• Investigators: Principal Investigator: Ekaterini Boleti, Royal Free Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Actual): July 25, 2025
• Study Completion (Actual): July 25, 2025

Study Registration Dates

• First Submitted: February 9, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: predictive biomarker; immuno-oncology; cell culture; computer vision; functional testing; microtumor
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
• Other Study ID Numbers: PEAR-TREE2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Study Data/Documents

1. Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No