eligibility_summary
Adults 18–70 with measurable melanoma (after anti‑PD‑1/PD‑L1 ± CTLA‑4/LAG‑3, limited mucosal), NSCLC (after platinum + checkpoint and any needed targeted therapy), or HNSCC (1–3 prior lines incl platinum and anti‑PD‑1/PD‑L1). Needs resectable tumor for KSQ‑001EX, ECOG 0–1, adequate organs, washouts. Excludes: uveal melanoma, LCNEC NSCLC, active/untreated brain mets, autoimmune disease, active infections incl HIV/HBV/HCV, prior transplant/cell therapy, cardiac/pulmonary disease, steroids >10 mg, pregnancy, recent live vaccine, other active cancer.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Interventions: KSQ-001EX (autologous, gene‑edited tumor‑infiltrating lymphocyte therapy) plus lymphodepleting cyclophosphamide (alkylating agent) and fludarabine (purine analog), some patients also receive high‑dose interleukin‑2 (biologic cytokine). Mechanisms: KSQ-001EX T cells are engineered to inactivate SOCS1, lifting negative feedback on cytokine/JAK‑STAT signaling to boost T‑cell activation, proliferation, persistence, and cytotoxicity against tumor antigens. Cyclophosphamide and fludarabine create immune “space” and reduce regulatory/suppressive lymphocytes to promote TIL engraftment. IL‑2 drives T‑cell expansion and survival via IL‑2R/JAK‑STAT and PI3K/AKT. Targets: patient TILs, tumor cells in melanoma/NSCLC/HNSCC, pathways include SOCS1, JAK‑STAT, cytokine signaling, and IL‑2/IL‑2R.