A new PRAME-directed T-cell receptor (TCR) therapy is offering cautious optimism for patients with advanced uveal melanoma, a rare eye cancer with historically limited treatment options. Presented at the Presidential Session of the ESMO Congress 2025 in Berlin, phase 1 data on anzutresgene autoleucel (anzu-cel, also known as IMA203) demonstrated encouraging safety and meaningful antitumor activity in a heavily pretreated patient population.
During the presentation, Sapna Patel explained that PRAME is an intracellular antigen expressed in approximately 90% of uveal melanoma tumors. By engineering T cells to recognize the PRAME peptide presented on HLA-A*02:01 molecules, anzu-cel is designed to precisely target cancer cells while sparing healthy tissue. This approach is particularly notable given that uveal melanoma is considered a “cold” tumor, typically resistant to immunotherapy.
The trial included 16 patients with locally advanced or metastatic uveal melanoma, most of whom had liver and extrahepatic metastases and had already received multiple systemic and liver-directed treatments, including tebentafusp. Despite this, a single infusion of anzu-cel achieved a 67% objective response rate and an 88% disease control rate, with responses lasting a median of 11 months. Median progression-free survival reached 8.5 months, while overall survival had not yet been reached at the time of reporting.
Safety findings were consistent with expectations for TCR-based therapies. While cytopenias were common due to lymphodepleting chemotherapy, cytokine release syndrome occurred in all patients but was largely low-grade, manageable, and resolved without long-term complications. Importantly, no treatment-related deaths were reported.
Discussant John Haanen emphasized the significance of these results, noting the dismal prognosis typically faced by patients with metastatic uveal melanoma. While he cautioned that longer follow-up is needed to assess durability and potential for cure, the response rate observed with anzu-cel stands out in a field with few effective options.
Overall, these early results suggest PRAME-targeted TCR therapy could represent a meaningful advance for uveal melanoma patients, with a phase 2 extension study now underway to further validate these findings.