Immatics' PRAME Cell Therapy Shows Promise in Advanced Melanoma

Immatics, a German biotech company, has reported encouraging results from its phase 1b trial of IMA203, a cell therapy targeting preferentially expressed antigen in melanoma (PRAME). The data, presented at the American Society of Clinical Oncology (ASCO) conference in Chicago, demonstrates significant potential for patients with advanced melanoma who have previously undergone treatment.

Impressive Response Rates Across Melanoma Subtypes

The extended phase 1b follow-up included 33 patients with PD-1-refractory metastatic melanoma who had received a median of two prior lines of treatment. Among the 32 evaluable patients, IMA203 achieved a confirmed objective response rate (cORR) of 56%. Notably, the therapy showed efficacy across different melanoma subtypes:

• Cutaneous melanoma (14 patients): 50% cORR
• Uveal melanoma (16 patients): 67% cORR, including tebentafusp-refractory patients
• Mucosal melanoma (2 patients) and melanoma of unknown primary (1 patient) were also included in the study

Durability and Survival Outcomes

The trial results also highlighted the potential long-term benefits of IMA203:

• Median duration of response (mDOR) for all 33 patients: 12.1 months (median follow-up of 13.4 months)
• Median progression-free survival (PFS): 6.1 months
• Median overall survival (OS): 15.9 months

Patients with cutaneous melanoma showed particularly promising outcomes, with mDOR not reached at 16.7 months of follow-up. The uveal melanoma subgroup demonstrated a mDOR of 11 months at 13.4 months of follow-up and a median PFS of 8.5 months.

Safety Profile and Future Directions

The safety data, collected from 74 patients across phase 1a and 1b, indicated a manageable safety profile. The most common treatment-emergent adverse events were cytopenias associated with lymphodepletion. Cytokine release syndrome (CRS) events were mostly mild to moderate, with no grade 4 or 5 events related to IMA203 reported.

Based on these promising results, Immatics has initiated a phase 3 trial named SUPRAME. This open-label, randomized study will evaluate IMA203 against investigator's choice of treatment in approximately 360 patients with advanced or metastatic cutaneous melanoma who have previously received checkpoint inhibitor treatment. The primary endpoint is PFS, with secondary measures including OS, ORR, safety, and patient-reported quality of life outcomes.

Immatics plans to submit a full approval request to the FDA in the first quarter of 2027, bolstered by the regenerative medicine advanced therapy designation already secured for IMA203.