Abstract CT098: Preliminary report of the TUMORIN Trial (using ex vivo tumoroids to predict immunotherapy response in NSCLC)
Authors: Jared Ehrhar, Seth Currlin, Michelle Attaya, Jun Zhang, Rikhia Chakraborty
Journal: Cancer Research (2025)

Abstract Background: Immunotherapy has transformed non-small cell lung cancer (NSCLC) treatment, yet variability due to primary, adaptive, or acquired resistance remains a significant challenge. Addressing resistance mechanisms and identifying novel combinations with standard-of-care (SOC) immunotherapies is critical to improving outcomes. Nilogen’s 3D-EXplore platform preserves the tumor immune compartment and microenvironment (TIME), maintaining tumor heterogeneity and immune cells. This study evaluated the feasibility of Nilogen’s platform in advanced/metastatic NSCLC patients treated with immune checkpoint inhibitors to predict therapeutic response and identify promising immunotherapy combinations, particularly anti-PD-1/L1 ± anti-CTLA-4 agents. Methods: A phase 4, single-arm, translational study was conducted with IRB approval, adhering to FDA-approved SOC. Eligible patients (≥18 years) included immunotherapy-naïve advanced/metastatic NSCLC patients or those progressing on prior immunotherapy. Biopsies were used to create ex vivo tumoroids. These tumoroids were incubated with or without clinically relevant concentrations of each patient’s immunotherapy regimen for 3 days. Tumor cell death was quantified via Nilogen’s QTDA algorithm using confocal imaging. Cytokine changes in tumor-infiltrating immune cells were assessed via multiplex analysis, and TIME immune composition was characterized by flow cytometry with T-cell and Treg markers. Anticipating 25 patients to enroll in this study, the response rate to treatment will be scored for each parameter from 1 to 3 compared to baseline (1 = ≤30% response, 2 = 31-50% response, 3 = &amp;gt;50% response rate) and correlated with clinical outcomes (e.g., response by RECIST vs. resistance to treatment) and tumor PD-L1 levels using ordinal analysis and the exact Jonckheere-Terpstra test. Results: From 2022 to now, five advanced NSCLC patients with squamous cell carcinoma or adenocarcinoma were enrolled, all progressing on prior immunotherapy Progression-free survival (PFS) ranged from 2.4-10.6 months, with combination therapies yielding longer PFS. In ex vivo tumor cell-killing assays, pembrolizumab demonstrated the highest efficacy (40-78% tumor cell death) in tumoroids from four patients, outperforming other treatments. T-cell activation and cytokine profiling corroborated tumor cell-killing results. Tumor stage at recurrence was associated with diminished responses in advanced cases. Conclusion: Despite limited sample size precluding statistical correlation, Nilogen’s 3D-EXplore platform demonstrated its potential for predicting treatment outcomes and understanding tumor microenvironment dynamics. Findings suggest that tumor heterogeneity observed in core biopsy-derived tumoroids can provide insights applicable to the entire tumor mass. Citation Format: Jared Ehrhar, Seth Currlin, Michelle Attaya, Jun Zhang, Rikhia Chakraborty. Preliminary report of the TUMORIN Trial (using ex vivo tumoroids to predict immunotherapy response in NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT098.