PRAME-Directed T-Cell Receptor Therapy Demonstrates Durable Responses in Advanced Melanoma

Clinical Summary: 

• Design/Population: The ongoing phase 1/2 IMA203-101 study evaluated the autologous PRAME-directed T-cell receptor therapy anzu-cel in patients with advanced PRAME-positive, HLA-A*02:01–positive solid tumors. This analysis included 33 patients with advanced melanoma treated at the recommended phase 2 dose.
• Key Outcomes: Anzu-cel demonstrated a confirmed objective response rate of 56% with durable responses, a median duration of response of 14.6 months, and a manageable safety profile. Cytokine release syndrome was primarily low grade, while immune effector cell–associated neurotoxicity syndrome and hemophagocytic lymphohistiocytosis were uncommon.
• Clinical Relevance: These findings support PRAME-targeted T-cell receptor therapy as a promising treatment strategy for advanced melanoma and provide the rationale for the ongoing registration-directed phase 3 SUPRAME trial.

Diwakar Davar, MBBS, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, Pennsylvania, discusses results from the ongoing phase 1/2 IMA203-101 trial evaluating the PRAME-directed T-cell receptor therapy anzu-cel in patients with advanced melanoma. The study assessed the efficacy and safety of this one-time autologous cellular therapy in heavily pretreated patients with PRAME-positive, HLA-A*02:01–positive disease.

The study demonstrated encouraging and durable clinical activity across melanoma subtypes, including cutaneous and uveal melanoma, with responses occurring rapidly after treatment and a favorable safety profile consistent with T-cell receptor-based cellular therapy. Dr Davar also discusses how these findings support the continued development of anzu-cel in the ongoing phase 3 SUPRAME trial and highlight the broader potential of T-cell receptor therapies targeting intracellular tumor antigens.

Source:

Davar D, Patel SP, Hernandez-Aya LF, et al.  Patient-level clinical response dynamics in advanced melanoma with anzutresgene autoleucel (anzu-cel), a PRAME-directed T-cell receptor (TCR) T-cell therapy. Presented at the ASCO Annual Meeting; May 30–June 3, 2026; Chicago, Illinois. Abstract 9508.