The randomized Phase 3 SUPRAME trial evaluates IMA203 (anzutresgene autoleucel) – an autologous PRAME-directed TCR-T cell therapy – versus investigator's choice (nivolumab ± relatlimab, pembrolizumab, ipilimumab, lifileucel, or chemotherapy) in previously treated unresectable or metastatic cutaneous melanoma. IMA203 targets an intracellularly processed PRAME-derived peptide presented via HLA-A*02:01, triggering a highly specific cytotoxic T cell response; treatment is administered following lymphodepletion with cyclophosphamide/fludarabine and low-dose subcutaneous IL-2. Phase 1b data demonstrated a confirmed ORR of 56% with a median duration of response of 12.1 months in heavily pretreated patients. Key eligibility criteria include HLA-A*02:01-positive cutaneous melanoma (including acral), ECOG 0–1, progression on =1 prior PD-1 inhibitor, and prior BRAF ± MEK inhibitor therapy in BRAF-mutated patients.
The SUPRAME trial investigates a novel cell therapy called IMA203 in patients with advanced melanoma that has stopped responding to standard immunotherapy. The patient's own immune cells are collected, engineered in the laboratory to specifically attack a tumor marker called PRAME, and infused back after a short preparatory treatment. In an earlier study, more than half of patients responded to this therapy. Eligible patients must have a specific tissue type (HLA-A*02:01), good general health, and prior treatment with at least one checkpoint inhibitor.
