## Protocol Section
### Identification Module
**NCT ID:** NCT06264479

**Acronym:** PEAR-TREE2

**Brief Title:** Prospective Evaluation of AI R&D Tool for Patient Stratification: a Trial for Renal Immuno-oncology Model Experimental Evaluation 2

**Official Title:** Prospective Evaluation of AI R&D Tool for Patient Stratification: a Trial for Renal Immuno-oncology Model Experimental Evaluation 2

#### Organization Study ID Info
**ID:** PEAR-TREE2
#### Organization
**Class:** INDUSTRY
**Full Name:** Ourotech, Inc.
### Status Module
#### Completion Date
**Date:** 2029-03-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-04-02

**Type:** ACTUAL

**Last Update Submit Date:** 2024-04-01

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-09-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-02-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-02-09
**Study First Submit QC Date:** 2024-02-09
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Royal Free Hospital NHS Foundation Trust

**Class:** UNKNOWN

**Name:** Cambridge University Hospitals NHS Trust

**Class:** UNKNOWN

**Name:** East & North Herts NHS Trust

**Class:** OTHER

**Name:** Imperial College Healthcare NHS Trust

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Ourotech, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** 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).

**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.

### Conditions Module

**Conditions:**

- Kidney Cancer

- Renal Cell Cancer Metastatic

**Keywords:**

- computer vision

- cell culture

- microtumor

- functional testing

- predictive biomarker

- immuno-oncology

### Design Module

#### Bio Spec

**Description:** Tumor cores and blood

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 200

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients with advanced or metastatic kidney cancer, due to start a new line of systemic therapy (targeted drug, immunotherapy, etc.)

**Intervention Names:**

- Procedure: Biopsy

**Label:** Trial Cohort

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Trial Cohort

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

**Name:** Biopsy

**Type:** PROCEDURE

### Outcomes Module

#### Other Outcomes

**Description:** 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

**Measure:** Culture success rate

**Time Frame:** 4 days

**Description:** The hazard ratio for PFS and OS between Pear-assay biomarker-high and biomarker-low groups

**Measure:** Hazard ratio by biomarker group

**Time Frame:** 2 years

**Description:** The performance of Pear image-based biomarkers are established against patients overall survival.

**Measure:** OS prediction accuracy

**Time Frame:** 2 years

#### Primary Outcomes

**Description:** The sensitivity, specificity PPV and NPV of Pear image-based biomarkers are established against patient ORR (evaluated on imaging).

**Measure:** Objective Response Rate correlation accuracy (sensitivity & specificity)

**Time Frame:** 6 months

#### Secondary Outcomes

**Description:** The sensitivity, specificity PPV and NPV of Pear image-based biomarkers are established against patients achieving a complete response (evaluated by imaging).

**Measure:** Complete Response rate correlation accuracy (sensitivity & specificity)

**Time Frame:** 2 years

**Description:** The sensitivity, specificity PPV and NPV of Pear image-based biomarkers are established against patients achieving a deep response (evaluated by imaging).

**Measure:** Deep Response rate correlation accuracy (sensitivity & specificity)

**Time Frame:** 2 years

**Description:** 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).

**Measure:** Durable Response rate correlation accuracy (sensitivity & specificity)

**Time Frame:** 2 years

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

**Measure:** PFS prediction accuracy

**Time Frame:** 2 years

### Eligibility Module

**Eligibility Criteria:** 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

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

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

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** duleek@pearbio.com

**Name:** Duleek Ranatunga

**Phone:** +44 7716558079

**Role:** CONTACT

**Contact 2:**

**Email:** elli.tham@pearbio.com

**Name:** Elli Tham

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Cambridge

**Contacts:**

***Contact 1:***

- **Name:** Kate Fife

- **Role:** CONTACT

**Country:** United Kingdom

**Facility:** Addenbrooke's Hospital

**State:** Cambridgeshire

**Zip:** CB2 0QQ

**Location 2:**

**City:** London

**Contacts:**

***Contact 1:***

- **Name:** Anand Sharma

- **Role:** CONTACT

**Country:** United Kingdom

**Facility:** Mount Vernon Cancer Centre

**Zip:** HA6 2RN

**Location 3:**

**City:** London

**Country:** United Kingdom

**Facility:** Imperial College Healthcare NHS Trust

**Zip:** W6 8RF

**Location 4:**

**City:** London

**Contacts:**

***Contact 1:***

- **Name:** Ekaterini Boleti, MD PhD MRCP

- **Phone:** 020 7830 2396

- **Phone Ext:** 34476

- **Role:** CONTACT

**Country:** United Kingdom

**Facility:** Royal Free NHS Foundation Trust

#### Overall Officials

**Official 1:**

**Affiliation:** Royal Free Hospital NHS Foundation Trust

**Name:** Ekaterini Boleti

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**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.

**IPD Sharing:** NO

### References Module

#### Available IPDs

**Type:** Study Protocol

**URL:** https://www.pearbio.com/peartree2

## Document Section

### Large Document Module

#### Large Docs

- Date: 2023-07-28

- Filename: Prot_SAP_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 424039

- Type Abbrev: Prot_SAP

- Upload Date: 2023-07-28T07:18

- Date: 2023-07-28

- Filename: ICF_001.pdf

- Has ICF: True

- Has Protocol: False

- Has SAP: False

- Label: Informed Consent Form

- Size: 197013

- Type Abbrev: ICF

- Upload Date: 2023-07-28T07:19

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009369

- Term: Neoplasms

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000002277

- Term: Carcinoma

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000014571

- Term: Urologic Neoplasms

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000007674

- Term: Kidney Diseases

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M5548

- Name: Carcinoma, Renal Cell

- Relevance: HIGH

- As Found: Renal Cell Cancer

- ID: M10703

- Name: Kidney Neoplasms

- Relevance: HIGH

- As Found: Kidney Cancer

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M17320

- Name: Urologic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M10698

- Name: Kidney Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4906

- Name: Renal Cell Carcinoma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002292

- Term: Carcinoma, Renal Cell

- ID: D000007680

- Term: Kidney Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M2853

- Name: Immunomodulating Agents

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
