Immunocore reports updated Phase 1 data of brenetafusp (IMC-F106C), an ImmTAC bispecific targeting PRAME, in immune checkpoint pre-treated cutaneous melanoma patients at ASCO 2024

Core Insights - Immunocore has reported updated Phase 1 data for brenetafusp (IMC-F106C), an ImmTAC bispecific targeting PRAME, showing promising clinical activity in late-line cutaneous melanoma patients previously treated with immune checkpoint inhibitors [1][2][3] Phase 1 Clinical Data - Monotherapy with brenetafusp demonstrated a disease control rate (DCR) of 56%, with 4 patients achieving partial response (ORR 11%) and 16 patients showing stable disease [6] - The median progression-free survival (mPFS) for all patients was 4.2 months, with a notable difference in mPFS between PRAME positive (4.2 months) and PRAME negative patients (2.1 months) [7] - Among ctDNA-evaluable PRAME positive patients, 42% exhibited a molecular response, while no PRAME negative patients showed ctDNA reduction [7] Patient Population and Treatment Tolerance - A total of 47 patients received brenetafusp monotherapy, all of whom had prior exposure to immune checkpoint inhibitors, with 100% having received anti-PD1 and 81% anti-CTLA4 [4] - Brenetafusp was well tolerated, with manageable treatment-related adverse events (TRAEs) primarily consisting of Grade 1 or 2 cytokine release syndrome (CRS) and rash [5][8] Combination Therapy Insights - In a cohort of 9 patients receiving brenetafusp in combination with anti-PD1 (pembrolizumab), 4 achieved disease control, including 1 ongoing partial response [9] - The combination therapy was also well tolerated, with manageable TRAEs consistent with the mechanisms of both agents [8] Gene Expression and T Cell Fitness - A gene signature indicating systemic T cell fitness was identified, with patients above the median expression level showing a median PFS of 6 months and a DCR of 69% compared to 2 months and 42% for those below the median [10] Upcoming Trials and Presentations - Immunocore is currently enrolling patients in a Phase 3 clinical trial (PRISM-MEL-301) for brenetafusp combined with nivolumab in first-line advanced cutaneous melanoma, with the primary endpoint being progression-free survival [12][17] - The advanced cutaneous melanoma data from the ongoing Phase 1/2 trial will be presented at the 2024 ASCO Annual Meeting [11]