eligibility_summary
Adults >=18 with refractory/recurrent injectable melanoma or SCCHN after >=6 wks prior PD-1/PD-L1 (progressed during/<=6 wks after), no curative options, >=15 mm injectable/biopsiable lesion, evaluable disease, ECOG 0-1, life expectancy >3 mo, adequate labs, contraception, consent. Exclude: transplant/immunosuppression, anti-cancer therapy <30 d or radiation <14 d, other invasive cancer <5 y, major CV/ILD/hepatic/HIV/active infection, LDH >3x ULN (melanoma), PPI/antibiotics at screening, coagulation disorder/anticoagulants <10 d, pregnancy/breastfeeding, untreated brain mets, allergy to TILT-123/avelumab, substance abuse, live vaccine <30 d, prior severe irAEs.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase I, open-label, single-arm dose-escalation in melanoma and SCCHN progressing after anti‑PD(L)1. Interventions: TILT‑123 (biological oncolytic adenovirus, Ad5/3‑E2F‑d24 encoding human TNF‑α and IL‑2) plus avelumab (anti‑PD‑L1 IgG1 monoclonal antibody). Mechanisms: TILT‑123 selectively replicates in tumor cells (tumor‑selective E2F/d24 control), causing oncolysis and local expression of TNF‑α and IL‑2 to inflame the tumor microenvironment, enhance dendritic cell priming, and activate/expand cytotoxic T cells and NK cells, improving immune infiltration. Avelumab blocks PD‑L1 to restore T‑cell function and may engage ADCC. Targets/pathways: tumor cells (oncolysis), E2F/d24 tumor selectivity, TNF and IL‑2 signaling, PD‑1/PD‑L1 axis, key cells include CD8+ T cells, NK cells, dendritic cells, and tumor vasculature.