Immatics' investigational T-cell therapy, IMA203, targeting preferentially expressed antigen in melanoma (PRAME), has shown promising clinical activity in patients with previously treated metastatic melanoma. Data from a phase 1 trial (NCT03686124) presented at the 2024 Society for Melanoma Research Congress revealed a confirmed objective response rate (ORR) of 54% (14 out of 26 patients). These findings support the initiation of a phase 3 trial to further evaluate the agent's efficacy.
The study's results indicated a median duration of response (DOR) of 12.1 months (range, 4.2 to 25.5+ months). Notably, 7 of the 14 patients who achieved a confirmed response were still experiencing ongoing responses at the time of data analysis (cutoff date: August 23, 2024).
Efficacy and Survival Outcomes
In the dose-escalation phase of the trial, the median progression-free survival (PFS) was 2.6 months, and the median overall survival (OS) was 6.3 months. The dose-expansion phase demonstrated a median PFS of 6.0 months (range, 0.3+ to 26.8+ months), while the median OS was not reached (NR; range, 0.3+ to 26.8+ months). Investigators observed a statistically significant difference in both PFS (P < .0001) and OS (P = .0003) between the dose-escalation and dose-expansion phases within the melanoma cohort. Among patients in the dose-expansion phase who experienced a 50% or greater reduction in tumor size, the median PFS was 13.4 months.
Safety and Tolerability
The safety analysis included 70 patients. Cytopenias associated with lymphodepletion were the most frequently observed toxicities. Cytokine release syndrome (CRS) was reported as grade 1 (37%), grade 2 (46%), and grade 3 (11%). Immune effector cell-associated neurotoxicity (ICANS) occurred at grade 1 (6%), grade 2 (4%), and grade 3 (4%). No deaths were attributed to the study treatment. The tolerability profile of IMA203 in melanoma patients was generally consistent with prior reports of the agent's monotherapy safety.
The recommended phase 2 dose was determined to be 1 x 10^9 to 10 x 10^9 TCR-T cells.
SUPRAME Phase 3 Trial
Based on these encouraging results, Immatics is planning to launch the registration-enabling, randomized phase 3 SUPRAME trial in December 2024. This trial will enroll approximately 360 patients with unresectable or metastatic melanoma who have previously been treated with a checkpoint inhibitor. Participants will be randomized 1:1 to receive either IMA203 (n = 180) or the investigator's choice of selected approved agents (n = 180).
The primary endpoint of the SUPRAME trial is PFS. Secondary endpoints include safety, ORR, DOR, OS, and patient-reported outcomes. An interim analysis is planned after approximately 200 patients have been enrolled. Patient enrollment is expected to be completed by late 2026.
According to Martin Wermke, MD, of the National Center for Tumor Diseases Dresden, the observed tumor shrinkage, durable responses, and meaningful PFS and OS outcomes after a single treatment with ACTengine® IMA203 in heavily pretreated metastatic melanoma patients highlight the potential impact of IMA203. He stated that these results provide a strong rationale for accelerating the late-stage clinical development of this product candidate.
