Using Ex Vivo Tumoroids To Predict Immunotherapy Response In NSCLC

Recruiting

• Conditions: Lung Cancer; NSCLC; NSCLC Stage IV

• Registration Number: NCT05332925
• Lead Sponsor: Jun Zhang, MD, PhD

Brief Summary

To test whether it is feasible to perform the 3D-EX functional predictive response bioassay in the context of patients with advanced/metastatic NSCLC receiving immune checkpoint inhibitors in the standard of care clinical setting.

Detailed Description

Non-small cell lung cancer (NSCLC), which accounts for approximately 85% of all lung cancer cases, remains the leading cause of cancer death worldwide. Immunotherapy such as using immune checkpoint inhibitors (ICIs) to target the programmed death-1 and its ligand (PD-1/L1) has revolutionized our management of this deadly disease.

However, a large proportion of patients do not derive benefit due to primary, adaptive or acquired resistance. Hence, better identifying this patient population, understanding the resistance mechanism and exploring novel combinations with current SOC immunotherapy are urgently needed to continue to benefit our NSCLC patients.

The investigators hypothesize that patient-derived immune cell containing ex-vivo tumoroids could serve these purposes. In this study, the investigators plan to develop such a 3D ex-vivo system utilizing fresh biopsied tissue from NSCLC patients. The investigators plan to prospectively evaluate the value of these ex-vivo tumoroids in immunotherapy naive advanced/metastatic NSCLC patients who will be receiving anti-PD-1/L1 (with or without anti-CTLA-4) per standard-of-care.

Study Timeline

• Study First Submitted: 2022-04-10
• Study First Submitted QC: 2022-04-10
• Study First Posted: 2022-04-18
• Study Start: 2022-07-21
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-21
• Last Update Posted: 2024-02-23
• Primary Completion: 2026-01
• Study Completion: 2027-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Patients with advanced/metastatic NSCLC
• Must be immunotherapy naive
• Males and females age ≥ 18 years
• ECOG Performance Status 0 - 2
• Measurable disease by RECIST 1.1
• Must have a lesion (either primary or metastatic lesion) that can be safely biopsied to have sufficient tissue (at minimum, 3-4 cores using 20g or larger core biopsy) to generate tumoroids
• Must have at least one target lesion to evaluate treatment response
• Will be receiving anti-PD-1/L1 with or without anti-CTLA-4 per standard of care Adequate organ function defined per standard of care in this setting.
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception as required/recommended by each immune checkpoint inhibitor used in the setting of standard of care.

Exclusion Criteria

• Incarcerated
• Not competent to make medical decision, noncommunicative or noncompliant per investigator's judgement.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Feasibility of establishing 3D ex-vivo tumoroid model	2 years	Twenty-five patients will be enrolled. The bioassay will be considered to be feasible if the 3D Ex-Vivo assay results are obtained on at least 20 patients.

Secondary Outcome Measures

Name	Time	Method
Correlation of response in ex vivo tumoroids with clinical objective response	2 years	To test whether the 3D-EX functional response bioassay can predict tumor response (using RECIST v1.1) in patients with advanced/metastatic NSCLC, receiving treatment with immune checkpoint inhibitors, in a standard clinical setting.

Trial Locations

Locations (2)

The University of Kansas Cancer Center (KUCC); 🇺🇸 Fairway, Kansas, United States

The University of Kansas Cancer Center, Westwood Campus; 🇺🇸 Kansas City, Kansas, United States