eligibility_summary
Adults >18 with unresectable/metastatic solid tumors progressed on standard therapy, >=1 lesion >=1 cm for outpatient TIL harvest, ECOG 0-1, adequate marrow/liver/renal, >=1 prior line, tumor-specific: (HNSCC: platinum + PD-1/PD-L1, melanoma: PD-1 +/- CTLA-4/LAG-3, actionables progressed). Exclude active CNS mets (treated stable, no WBRT), autoimmune/immunosuppression, recent infection/therapy, cardiac ischemia, poor PFTs, antibiotic allergy, no DP CD8 TIL, other active cancers <3y.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Phase I randomized open-label trial in advanced solid tumors tests two autologous adoptive cell therapies: 1) AGX148: CD39+CD103+ CD8+ tumor-infiltrating lymphocytes (TIL), 2) AGX148/PH-762: same TIL expanded ex vivo with PH-762, a siRNA that transiently knocks down PD-1. Regimen includes lymphodepleting cyclophosphamide + fludarabine and IL-2 support (high-dose IV then low-dose SC). Mechanisms/types: AGX148 (cellular therapy) enriches tumor-reactive cytotoxic T cells via CD39/CD103 selection, PH-762 (gene-silencing siRNA) decreases PD-1 checkpoint signaling, IL-2 (cytokine) promotes T-cell proliferation/survival, cyclophosphamide (alkylator) and fludarabine (purine analog) enhance engraftment. Targets/pathways: tumor antigens via TCR on DP CD8 TIL, PD-1/PD-L1 axis, IL-2/IL-2R signaling, CD39/ENTPD1 and CD103/ITGAE mark the tumor-reactive subset.