eligibility_summary
Adults (≥18) with advanced melanoma (non-uveal), NSCLC, HNSCC, CRC, PDAC, or cervical cancer after 1–4 prior lines (incl platinum/IO, targeted therapy if actionable). Need resectable tumor for KSQ-004EX and ≥1 measurable lesion post-resection, ECOG 0–1, adequate marrow/renal/hepatic, washouts, contraception. Exclude prior transplant/cell therapy, significant autoimmune/infection, untreated brain mets, ascites, HIV/HBV/HCV, >10 mg steroids, cardiac/QTc/pulmonary disease, pregnancy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Phase 1/2 single-arm study of KSQ-004EX, an autologous, gene-edited tumor-infiltrating lymphocyte (TIL) therapy (cellular immunotherapy, IV) engineered to inactivate SOCS1 and Regnase-1. Mechanism: removing intrinsic brakes on T-cell function—SOCS1 suppresses JAK-STAT cytokine signaling, Regnase-1 (ZC3H12A) is an RNase that degrades activation/cytokine mRNAs—thereby enhancing T-cell activation, cytokine production, proliferation, persistence, and tumor killing. All patients receive lymphodepletion with cyclophosphamide (alkylating agent) and fludarabine (purine antimetabolite) to deplete host lymphocytes and increase homeostatic cytokines for engraftment, one arm adds interleukin-2 (cytokine) to support T-cell expansion. Targets: autologous TILs recognizing tumor neoantigens, pathways: JAK-STAT/cytokine signaling and immune mRNA stability within T cells.