ESMO 2025 | IMA203, a PRAME-directed TCR therapy, shows promise in uveal melanoma

The major result in melanoma and other skin cancers has been presented in uveal melanoma. It’s a tumor of the eye. It’s the most common tumor of the adult eye. In this case, at a presidential session, the results of a phase one study have been presented. It’s very uncommon to have a phase one study at the presidential session. That was because the results were absolutely unprecedented. We have seen a cell therapy which is called IMA203, a PRAME-directed TCR therapy, shows promise in uveal melanoma. It’s a gene-engineered cell therapy with a TCR that recognizes PRAME, which is an antigen highly expressed in uveal melanoma. What these trials have shown is a 67% confirmed objective response rate, which is much higher than anything else that we have seen in this disease, which is a rare disease – very few people have it, so it’s also difficult to conduct trials. And this cell therapy is something that we will for sure hear much more about in the future. It’s complex, as all cell therapies, in manufacturing and administration, but it’s a one-time treatment. The toxicities are significant because it’s given together with lymphodepleting chemotherapy, and the cells themselves can also induce some toxicities, like cytokine release syndrome, but everything is confined to the weeks of the treatment, and after that, you get the treatment and then you’re off. So, if the responses, as we have seen, can be very durable – years – so far, we have seen a shorter follow-up; median duration of response was 11 months. If some of these responses are durable for years, then we might see, for the first time, some patients with uveal melanoma being cured. That’s the hope for the future.

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