eligibility_summary
Eligibility: Adults (>=18) with incurable metastatic/locoregional epithelial cancers, ECOG 0-2, adequate labs, life expectancy >12 wks, and Tran Lab-confirmed neoantigen-reactive TCR(s). Controlled HBV/HCV/HIV allowed. Negative pregnancy test and contraception required. Exclude: concurrent/recent trials or anticancer therapy (incl anti-CD40), recent major surgery/radiation, organ transplant, pneumonitis/ILD, uncontrolled illness, untreated CNS mets, active autoimmune on >10 mg steroids, live vaccines, major CV disease, unresolved >=G2 AEs, pregnancy, noncompliance.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Phase I/Ib single-arm study in incurable epithelial cancers testing: 1) Autologous TCR-transduced T cells (cell therapy) engineered to express patient-specific TCRs against 1–5 tumor-specific neoantigen peptides presented by HLA, enabling antigen-specific T-cell activation and tumor cell killing, 2) CDX-1140 (agonist monoclonal antibody, fully human IgG2κ) targeting CD40 to activate dendritic cells/macrophages/B cells, enhancing antigen presentation and costimulation, 3) Pembrolizumab (humanized IgG4 monoclonal antibody) blocking PD-1 to reverse T-cell exhaustion and sustain effector function. Targets/pathways: tumor neoantigen–HLA complexes on tumor cells, TCR signaling on infused T cells, CD40 pathway on antigen-presenting cells, and PD-1 checkpoint on T cells. Optional repeat infusion may use gemcitabine plus cyclophosphamide/epirubicin to induce immunogenic cell death and transient lymphopenia.