Findings from an ongoing phase 1a/b trial show that IMA203, a PRAME-directed T-cell receptor therapy, demonstrates high response rates and durable disease control in a heavily pretreated population of patients with metastatic uveal melanoma. 

These findings, presented by Sapna Patel, MD, University of Colorado, Anschutz, Colorado, at the 2025 European Society for Medical Oncology (ESMO) Congress, position IMA203 as a promising next-generation immunotherapy approach for PRAME-expressing uveal melanoma.

The trial enrolled 74 heavily pretreated patients with HLA-A*02:01–positive, PRAME-positive recurrent or refractory solid tumors with no available standard of care options, including patients with metastatic uveal melanoma with no prior tebentafusp exposure (n = 16). Following leukapheresis and manufacture of IMA203, patients underwent 4 days of lymphodepletion with 500 mg/ m² of cyclophosphamide and 30 mg/m² of ludarabine followed by IMA203 and low-dose interleukin-2 (1 million IU once daily for 5 days then twice daily for 5 days). 

The primary trial end point was safety in patients with uveal melanoma. Key secondary end points included objective response, duration of response, progression-free survival (PFS), and overall survival (OS). 

At analysis, the most common treatment-emergent events included cytopenias and cytokine release syndrome. Confirmed objective response was observed in 67% of patients and all patients experienced tumor shrinkage. Median duration of response was 11 months and 50% of confirmed responses were ongoing at a median follow-up of 13.4 months. Median PFS was 8.5 months and median OS was 16.2 months. Rapid engraftment was observed with a median T_max of 3 days and there was a sustained persistence of T-cells for up to 903 days. 

“IMA203 has a high degree of activity in pts with [uveal melanoma],” concluded Dr Patel et al. “Further study in a larger [uveal melanoma] cohort is warranted and planned.” 

Source:

Patel SP, Tsimberidou AM, Luke JJ, et al. Efficacy and safety of IMA203, a PRAME-directed T-cell receptor (TCR) T-cell therapy, in patients with previously treated advanced or metastatic uveal melanoma from a phase I trial. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. 1600O