Houston, TX - At the 2024 Society for Immunotherapy of Cancer Annual Meeting (SITC), results from the phase 1 IMA203-101 study (NCT03686124) revealed that IMA203, an investigational T-cell therapy targeting preferentially expressed antigen in melanoma (PRAME), induced sustained responses in patients with melanoma and other solid tumors. The data suggest a favorable tolerability profile and warrant further investigation in a phase 3 trial.
Robust Responses in Melanoma Subtypes
IMA203 demonstrated notable efficacy in melanoma, with a confirmed overall response rate (ORR) of 54% in cutaneous melanoma (n = 13) and 60% in uveal melanoma (n = 10). Unconfirmed ORRs were 62% and 60% respectively. Tumor shrinkage was observed in 85% of cutaneous melanoma patients and 100% of uveal melanoma patients. The disease control rate (DCR) at week 6 was 92% and 90% for cutaneous and uveal melanoma, respectively.
Activity Across Various Solid Tumors
Beyond melanoma, IMA203 showed activity in other solid tumors. One out of three patients with other types of melanoma, two out of four with ovarian cancer, one out of three with synovial sarcoma, and one out of six with other types of disease achieved a confirmed objective response. Tumor shrinkage was observed in 2 of 3, 3 of 4, 3 of 3, and 5 of 6 patients across each group, respectively. Disease control at week 6 was achieved in 3 of 3, 2 of 4, 3 of 3, and 5 of 6 patients, respectively.
Duration of Response and Future Trial
The median duration of response (DOR) in the melanoma cohort was 12.1 months (range, 4.2 to 25.5+). Notably, one patient maintained a response for over 26 months, and another for 24 months. According to Martin Wermke, MD, of the National Center for Tumor Early Clinical Trial Unit of University Hospital Dresden, Germany, these results justify a phase 3 trial, which is expected to commence by the end of 2024.
Mechanism of Action and Rationale
IMA203 is designed as autologous T cells transduced with PRAME-specific T-cell receptors. It targets HLA-A*02:01–presented PRAME peptides, utilizing CD8-positive T cells to specifically recognize and eliminate tumor cells expressing PRAME. PRAME is considered an ideal target for anti-cancer immunotherapy due to its prevalence in various solid tumors, including melanoma, lung cancer, and gynecologic malignancies. Its high target density and homogenous expression profile may minimize off-target toxicity.
Safety Profile
The safety analysis included 70 patients. In the phase 1a dose-escalation phase, 28 patients received IMA203 across four dose levels. In the phase 1b dose-expansion phase, 42 patients received the agent at dose levels 4 and 5; the efficacy population consisted of 41 patients. Grade 3 or higher blood and lymphatic system disorders, primarily neutropenia (88.6%), lymphopenia (55.7%), and leukopenia (54.3%), were observed in all patients. Grade 3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) affected 11% and 4% of patients, respectively. No grade 4 events of CRS and ICANS, or grade 5 toxicities, were reported.
