Immatics presented updated Phase 1b clinical data for its ACTengine® IMA203 TCR-T therapy at the Society of Melanoma Research Congress, showcasing promising efficacy and a manageable safety profile in heavily pretreated metastatic melanoma patients. The data support the advancement of IMA203 into a Phase 3 trial, with plans for global regulatory approval.
Phase 1 Trial Results
The Phase 1 trial included a dose-escalation phase (n=28) and a dose-expansion phase (n=42). In the melanoma efficacy population (n=28) from the dose-expansion phase, the confirmed objective response rate was 54%. Notably, 88% of patients experienced tumor shrinkage. The median duration of response was 12.1 months.
Median progression-free survival (PFS) in the dose-escalation phase for melanoma patients (n=11) was 2.6 months, increasing to 6.0 months in the dose-expansion phase (n=28; P < .0001). Median overall survival (OS) in the dose-escalation phase was 6.3 months and was not reached in the dose-expansion phase (n=28; P = .0003). Among patients with deep responses (≥50% tumor reduction, n=12), the median PFS was 13.4 months (P = .0033).
Safety Profile
The most frequent adverse events (AEs) were expected cytopenias associated with lymphodepletion, mild to moderate cytokine release syndrome (Grade 1, 37%; Grade 2, 46%; Grade 3, 11%), and infrequent immune effector cell-associated neurotoxicity syndrome (Grade 1, 6%; Grade 2, 4%; Grade 3, 4%). No treatment-related deaths were reported.
Mechanism of Action and Trial Design
IMA203 is a TCR-T therapy targeting an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in various solid cancers. The recommended Phase 2 dose was 1-10 × 10^9 TCR-T cells.
Prior to the Phase 1b portion of the trial, Immatics implemented manufacturing improvements to enhance key features of the treatment, including a T-cell enrichment process. All patients in the dose-expansion phase received the updated version of IMA203.
Correlations Between Dose, Exposure, and Clinical Outcomes
Consistent associations and correlations were observed between dose exposure, biological data, and clinical outcomes. Specifically, the IMA203 T-cell dose was significantly associated with confirmed clinical responses (P = .02) and correlated with T-cell peak level (Cmax, r = 0.84; P = 1.6 × 10^-18). T-cell peak level (Cmax, P = .05) and T-cell exposure (AUC0-28d, P = .05) were also associated with confirmed clinical responses.
SUPRAME Phase 3 Trial
Based on the Phase 1b data and discussions with the FDA, Immatics is proceeding directly to a registration-enabling Phase 3 trial, SUPRAME. The trial will be a global effort with sites in the United States and Europe. Immatics anticipates seeking a biologics license application (BLA) approval in the United States in early 2027. The primary endpoint for full approval will be progression-free survival.
"Observing significant tumor shrinkage and durable responses combined with meaningful progression-free survival and overall survival outcomes after a single treatment with ACTengine IMA203 in this patient population that have all exhausted multiple lines of systemic treatments illustrates the impact IMA203 can have on metastatic melanoma patients," said Martin Wermke, MD, coordinating investigator of the ACTengine IMA203 TCR-T trial.
Cedrik Britten, MD, the chief medical officer at Immatics, added, "We believe the presentation of this data set in conjunction with our recent meeting with the FDA, which has resulted in a pivotal trial design with progression-free survival as the primary endpoint for full approval, positions us to advance the development of IMA203 in the second-line or later metastatic melanoma setting."
