Dr Luke on the Role of IMA203 in Previously Treated Advanced Cutaneous Melanoma

“In this population of patients that had no available standard therapy, we saw more than half [achieving] long-term response, and that is very, very promising.”

Jason Luke, MD, associate director for clinical research and director of the Immunotherapy and Drug Development Center at Hillman Cancer Center, University of Pittsburgh, discussed the design and potential clinical effects of the phase 3 SUPRAME trial (NCT06743126), which is evaluating the efficacy of IMA203, a T-cell receptor–transduced T-cell therapy (TCR-T), vs investigator’s choice of standard therapy in patients with previously treated advanced cutaneous melanoma.

Luke explained that SUPRAME represents the first randomized phase 3 trial in solid tumors directly comparing a TCR-T-cell therapy with conventional systemic treatment in a refractory setting. In the trial, patients are randomly assigned to receive either IMA203 or the treating physician’s choice of standard therapy, Luke explains.

This study builds upon findings from the prior phase 1 IMA203-101 trial (NCT03686124) of IMA203, in which a cohort of 14 patients with cutaneous melanoma achieved a confirmed objective response rate of 50%. The median duration of response was not reached (range, 4.2-32.6+), and the median progression-free survival was 6.0 months (range, 1.4-34.0+).

Luke noted that the platform has several advantages over tumor-infiltrating lymphocyte (TIL)–based therapies. Whereas TIL therapy requires tumor resection and ex vivo expansion of tumor-resident lymphocytes, IMA203 relies on leukapheresis followed by peripheral T-cell engineering using lentiviral transduction. This circumvents the need for surgical tumor acquisition and allows for more streamlined production. Additionally, IMA203 does not require the administration of high-dose IL-2, which is typically necessary for TIL-based protocols and is associated with considerable toxicity.

Both TCR-T and TIL therapies require lymphodepleting chemotherapy prior to infusion, but the omission of IL-2 with IMA203 may improve tolerability. According to Luke, these operational and toxicity advantages, coupled with the early efficacy signal, suggest that TCR-T-cell therapies such as IMA203 may represent a next-generation option in the melanoma cell therapy landscape.