eligibility_summary
Inclusion: Adults (≥18) able to consent with advanced/metastatic solid tumors (NSCLC, CRC, HNSCC, pancreatic, breast, ovarian, or other) with TP53 R175H and HLA‑A02:01+, after ≥1 SOC line, measurable disease (RECIST 1.1), ECOG 0–1, adequate organ function. Exclusion: recent other cancer, active CNS primary, prior cell/gene or transplant, recent stroke/cardiac disease/HF, recent systemic therapy, key drug allergies, immunodeficiency, recent live vaccine, steroid‑treated immune disease, lactation, Li‑Fraumeni.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Intervention: NT-175, an autologous, gene‑engineered TCR-T cell therapy. Patients receive lymphodepleting fludarabine (purine analog antimetabolite) and cyclophosphamide (alkylating agent) pre-conditioning, a single NT-175 infusion, then recombinant IL-2 (cytokine) support. Mechanism: NT-175 expresses an HLA‑A02:01‑restricted T-cell receptor that specifically recognizes the TP53 R175H mutant peptide presented on tumor MHC class I, triggering antigen‑specific T-cell activation and cytotoxic tumor killing, lymphodepletion enhances engraftment, and IL‑2 promotes T-cell expansion/persistence. Targets: tumor cells harboring TP53 R175H and HLA‑A02:01, immune pathways include TCR–peptide–MHC I recognition, cytotoxic T-cell effector function, and IL‑2 signaling. Phase 1 in multiple advanced solid tumors.