eligibility_summary
Include: Adults (≥18) with measurable advanced/metastatic solid tumor, ECOG 0–1, HCC Child‑Pugh A, adequate organs, tissue/biopsy, able to swallow VGCV, contraception. Expansion: HCC/cutaneous ≤2 prior systemic, breast ≤2 cytotoxic. Intratumoral: cutaneous cancers with injectable lesion + distant mets, no prior oncolytic. Exclude: recent therapy/surgery/RT/live vaccine, unresolved >G1 AEs, active/unstable CNS disease, infection, malabsorption, ganciclovir contraindication, active HBV (HCC), HCV on antivirals, HIV+, steroids ≥10 mg/d.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Phase 1 study in advanced solid tumors testing GEN2 (non-replicating, off-the-shelf gene therapy vector, biologic) plus valganciclovir (small-molecule antiviral prodrug). GEN2 delivers two transgenes: HSV-enhanced thymidine kinase (HSV‑eTK, suicide gene) and human GM‑CSF. After GEN2 administration (IV or intratumoral), valganciclovir is phosphorylated by HSV‑eTK in transduced tumor cells, causing selective tumor cell death and immunogenic neoantigen release. GM‑CSF recruits/activates myeloid antigen-presenting cells (dendritic cells, macrophages), boosting antigen presentation and priming/expanding tumor-specific cytotoxic T cells, with potential NK involvement and systemic (abscopal) anti-tumor immunity. Targets/pathways: tumor cells via HSV‑eTK/valganciclovir cytotoxic pathway, GM‑CSF signaling on myeloid APCs, downstream activation of CD8+ T-cell responses.