eligibility_summary
Adults 18–75 with metastatic/recurrent HPV18+ solid tumors, failed prior therapy, HLA‑DRB10901, ECOG ≤1, ≥3‑mo survival, measurable disease, and adequate organ function (counts, liver, renal, coagulation, LVEF≥50%, SpO2≥92%). Contraception required, negative HCG pre‑apheresis. Exclude: allergies to study drugs, recent tx/surgery/vaccines/trials/cell therapy, unresolved tox, symptomatic CNS mets, uncontrolled disease/infection/autoimmunity/immunosuppression, other cancers, recent VTE, HIV/syphilis/HBV/HCV, transplants, active TB, pregnancy, poor compliance.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
NCT05952947 tests HRYZ-T101, an autologous TCR-engineered T cell therapy (biological, TCR-T) for HPV18-positive solid tumors. Patients receive lymphodepletion with fludarabine (purine analog, DNA synthesis inhibitor/immunosuppressant) and cyclophosphamide (alkylating agent) before a single IV TCR-T infusion. Mechanism: HRYZ-T101 T cells express a TCR recognizing an HPV18-derived peptide presented by HLA-DRB10901, triggering TCR signaling, cytokine release, and cytotoxic killing (perforin/granzyme) of HPV18+ tumor cells. Lymphodepletion reduces endogenous lymphocytes/Tregs and enhances TCR-T engraftment/persistence. Targeted cells/pathways: HPV18 antigen–expressing tumor cells (cervix, head/neck, anus, vulva, vagina, penis), HLA class II antigen presentation, adaptive T cell cytotoxic pathway. Phase I, single-arm dose escalation to determine RP2D.