eligibility_summary
Key eligibility: Histologically confirmed SS (age 2–17), MPNST/neuroblastoma/OS (2–21), weight ≥10 kg, prior systemic chemo, measurable disease, HLA‑A02 positive (not A02:05 or equivalent), tumor MAGE‑A4+, ECOG 0–1 (≥16) or Lansky ≥80 (2–16), life expectancy >3 mo. Exclude: hypersensitivity to fludarabine/cyclophosphamide, autoimmune disease, CNS mets, other active cancer, major CV disease, HIV/HBV/HCV/HTLV, pregnancy/breastfeeding, rapidly progressive disease.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
NCT05642455 (SPEARHEAD-3) tests afamitresgene autoleucel (afami-cel), an autologous, genetically modified TCR-T cell therapy. Patient T cells are engineered ex vivo to express an affinity‑enhanced T‑cell receptor that recognizes a MAGE‑A4 peptide presented by HLA‑A02, then given as a single IV infusion (weight‑based). Mechanism: upon binding MAGE‑A4/HLA‑A02 on tumor cells, the engineered T cells activate TCR/CD3 signaling, release perforin/granzymes and cytokines, and mediate targeted cytotoxicity. Targets: the cancer‑testis antigen MAGE‑A4 on tumor cells and the HLA‑A02 antigen presentation pathway. Population: pediatric/AYA with MAGE‑A4+ synovial sarcoma, MPNST, neuroblastoma, or osteosarcoma, requires HLA‑A02 and excludes HLA‑A02:05.