Observational Basket Trial to Collect Tissue to Train and Validate a Live Tumor Diagnostic Platform (CYBRID-02)

• ClinicalTrials.gov Identifier: NCT05520099
• Recruitment Status: Recruiting
• First Posted: August 29, 2022
• Last Update Posted: March 7, 2024
• Sponsor: Elephas
• Collaborator: Hoosier Cancer Research Network
• Information provided by (Responsible Party): Elephas

Tracking Information

• First Submitted Date: August 26, 2022
• First Posted Date: August 29, 2022
• Last Update Posted Date: March 7, 2024
• Actual Study Start Date: June 26, 2023
• Estimated Primary Completion Date: January 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2022)

Sensitivity and Specificity of Cybrid Score for Predicting In-Vivo Clinical Response to Immune Checkpoint Inhibitors [ Time Frame: 3 years ]

The ex-vivo prognostic accuracy of the Cybrid live tumor diagnostic platform will be determined using in-vivo RECIST 1.1 as the reference method.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 16, 2023)

Determine the Area Under the Receiver Operating Characteristic Curve (AUC) of Cybrid Score and Compare to the AUCs of Current FDA Approved Predictive Biomarkers PD-L1 and Tumor Mutation Burden (TMB) [ Time Frame: 3 years ]

The AUC of Cybrid Score will be established with a clinically meaningful confidence interval and compared to the AUCs of established FDA approved biomarkers for predicting clinical response to ICIs.

Original Secondary Outcome Measures (submitted: August 26, 2022)

Determine the Area Under the Receiver Operating Characteristic Curve (AUC) of Cybrid Score and Compare to the AUCs of Current FDA Approved Predictive Biomarkers PD-L1 and Tumor Mutation Burden (TMB) [ Time Frame: 3 years ]

The AUC of Cybrid Score will be established with a clinically meaningful confidence interval and compared to the AUCs of established FDA approved biomarkers for predicting clinical response to CPIs.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Observational Basket Trial to Collect Tissue to Train and Validate a Live Tumor Diagnostic Platform
• Official Title: Observational Basket Trial to Collect Tissue to Train and Validate a Live Tumor Diagnostic Platform (CYBRID-02)
• Brief Summary: The primary objective of this study is to determine the ex-vivo prognostic accuracy of the Cybrid live tumor diagnostic platform across a basket of solid tumors, using in-vivo RECIST 1.1 as the reference method.

Detailed Description

Cancer is a leading cause of death and despite many new drugs, a major diagnostic challenge remains knowing which drug will work best for a patient. A new class of drugs called checkpoint inhibitors (CPIs) have revolutionized cancer treatment. However, current diagnostic methods (e.g. PDL1, MSI and TMB) do not accurately predict which patients will respond.

Elephas is developing a diagnostic platform using small 3D Live Tumor Fragments (LTFs) from participants for accurate prediction of drug response with a focus on CPIs such as Pembrolizumab (Keytruda). These LTFs contain both tumor cells and infiltrating immune cells, which are critical in determining response to CPIs and other immunotherapies.

In this observational clinical basket trial, participants will be recruited and their actual clinical response (using RECIST 1.1) to CPIs across five solid tumors (lung, head/neck, bladder, kidney, and skin) will be compared to the platform's predictive Artificial Intelligence (AI) score that is based on RNA, clinical data, and 3D microscopy images. The sensitivity and specificity of the platform's score will be determined and compared to current diagnostic methods for CPIs like PDL1, MSI, and TMB.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Fresh tissue sample using core needle biopsy or forceps biopsy.

• Sampling Method: Non-Probability Sample

Study Population

Subjects suspected or diagnosed with Stage III or IV:

• Bladder: Urothelial Carcinoma (UC)
• Kidney: Clear Cell Renal Cell Carcinoma (ccRCC)

Subjects suspected or diagnosed with Stage IV/metastatic:

• Colon and Rectum: MSI-High/dMMR Colorectal Cancer (CRC)
• Head and Neck: Squamous Cell Carcinoma (HNSCC), excluding nasopharyngeal and salivary gland cancers
• Lung: Non-small cell lung cancer (NSCLC)
• Skin: Cutaneous Melanoma, excluding Uveal Melanoma
• Uterus: endometrial cancer

Subjects suspected or diagnosed with:

• Any metastatic solid tumor with high TMB, MSI-High or dMMR and are being considered for treatment with ICI therapy.
• Any metastatic solid tumor that the clinician plans to treat with ICI therapy.

Condition

• Colorectal Cancer
• Head and Neck Squamous Cell Carcinoma
• Non Small Cell Lung Cancer
• Cutaneous Melanoma
• Endometrial Cancer
• Urothelial Carcinoma
• Clear Cell Renal Cell Carcinoma

Intervention

Procedure: Core Needle or Forceps Biopsy

Subjects must be clinically able, at investigator discretion, to undergo additional core needle or forceps biopsy passes during their biopsy. These additional biopsies may either be collected from the primary tumor or a metastatic site amenable to additional passes (e.g., liver or lymph nodes) per the clinician.

Study Groups/Cohorts

Participants suspected of or diagnosed with Stage III or IV/metastatic cancer

Subjects suspected or diagnosed with Stage III or IV:

• Bladder: Urothelial Carcinoma (UC)
• Kidney: Clear Cell Renal Cell Carcinoma (ccRCC)

Subjects suspected or diagnosed with Stage IV/metastatic:

• Colon and Rectum: Microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) Colorectal Cancer (CRC)
• Head and Neck: Squamous Cell Carcinoma (HNSCC), excluding nasopharyngeal and salivary gland cancers
• Lung: Non-small cell lung cancer (NSCLC)
• Skin: Cutaneous Melanoma, excluding Uveal Melanoma
• Uterus: endometrial cancer

Subjects suspected or diagnosed with:

• Any metastatic solid tumor with high TMB, MSI-High or dMMR and are being considered for treatment with ICI therapy.
• Any metastatic solid tumor that the clinician plans to treat with ICI therapy.

Intervention: Procedure: Core Needle or Forceps Biopsy

Publications *

• Chen S, Zhang Z, Zheng X, Tao H, Zhang S, Ma J, Liu Z, Wang J, Qian Y, Cui P, Huang D, Huang Z, Wu Z, Hu Y. Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis. Front Oncol. 2021 Apr 16;11:562315. doi: 10.3389/fonc.2021.562315. eCollection 2021.
• Cherukuri AR, Lubner MG, Zea R, Hinshaw JL, Lubner SJ, Matkowskyj KA, Foltz ML, Pickhardt PJ. Tissue sampling in the era of precision medicine: comparison of percutaneous biopsies performed for clinical trials or tumor genomics versus routine clinical care. Abdom Radiol (NY). 2019 Jun;44(6):2074-2080. doi: 10.1007/s00261-018-1702-1.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 26, 2022): 216
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2027
• Estimated Primary Completion Date: January 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. Age ≥ 18 years at the time of consent.

3. Subjects must meet one of the following criteria:

   • Subjects suspected or diagnosed with Stage III or IV:

     • Bladder: Urothelial Carcinoma (UC)
     • Kidney: Clear Cell Renal Cell Carcinoma (ccRCC)

   • Subjects suspected or diagnosed with Stage IV/metastatic:

     • Colon and Rectum: Microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) Colorectal Cancer (CRC)
     • Head and Neck: Squamous Cell Carcinoma (HNSCC), excluding nasopharyngeal and salivary gland cancers
     • Lung: Non-small cell lung cancer (NSCLC)
     • Skin: Cutaneous Melanoma, excluding Uveal Melanoma
     • Uterus: endometrial cancer

   • Subjects suspected or diagnosed with:

     • Any metastatic solid tumor with high TMB, MSI-High or dMMR and are being considered for treatment with ICI therapy.
     • Any metastatic solid tumor that the clinician plans to treat with ICI therapy. NOTE: This can be either in the setting of a trial, compassionate use, or the use of appropriate LDT tests that per clinician, render the patient eligible for ICI therapy, either frontline or a later line.
4. Subjects must be clinically able, at investigator discretion, to undergo additional core needle or forceps biopsy passes during their biopsy.
5. Subjects who are newly diagnosed or have suspected cancer must be treatment-naïve at the time of biopsy. All other subjects should have the biopsy performed before starting their next line of treatment.
6. Subjects with a newly confirmed diagnosis who have previously undergone a standard of care biopsy must be willing to undergo a separate biopsy procedure solely for the purposes of this study.
7. Female subjects must not be pregnant.
8. Subjects with a known auto-immune disease that would render them ineligible for immune-oncology treatment are not eligible.
9. Immunocompromised subjects, and subjects known to be HIV positive and currently receiving antiretroviral therapy are not eligible. NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
10. Subjects who are enrolled or plan to be enrolled in a blinded oncology treatment trial are not eligible.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Catarina Costa; 609 955 4927; ClinicalTrials@elephas.com

Contact: Rae Richards; 317.634.5842 ext 38; rrichards@hoosiercancer.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05520099
• Other Study ID Numbers: HCRN BSK22-562
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Elephas
• Original Responsible Party: Jon Oliner, Elephas, Study Director
• Current Study Sponsor: Elephas
• Original Study Sponsor: Hoosier Cancer Research Network
• Collaborators: Hoosier Cancer Research Network

Investigators

• Study Director: Jon Oliner, MD, PhD; Elephas

• PRS Account: Elephas
• Verification Date: March 2024