Immunocore to Advance 160 mcg Brenetafusp after 87% Six-Month Survival
IMCR•Immunocore’s brenetafusp monotherapy achieved a 6-month overall survival rate of 87% and a 52% disease control rate in 66 heavily pretreated HLA-A*02:01-positive melanoma patients. These data support selecting a 160 mcg dose for the ongoing Phase 3 PRISM-MEL-301 first-line advanced melanoma trial.
1. Phase 1/2 Efficacy Data
In 66 patients treated with brenetafusp monotherapy at target doses of 20–320 mcg, median overall survival was 14.3 months (95% CI: 11.3–20.4) with 87% landmark OS at 6 months and 57% at 12 months. The disease control rate was 52% and overall response rate 12%, with numerically higher measures at the 160 mcg dose.
2. Safety and Tolerability
Brenetafusp displayed a predictable, mechanism-driven safety profile as monotherapy and in combination. Common treatment-related adverse events (≥20%) included low-grade cytokine release syndrome (56%), rash (44%), pyrexia (44%), chills (38%) and fatigue (31%), with transient Grade 3–4 lymphocyte count decreases in 25% and three discontinuations overall.
3. Subgroup and Biomarker Findings
Patients with primary PD-1 resistance showed a median OS of 14.7 months, comparable to the overall group, and a higher ctDNA response rate of 53% versus 38%. Exploratory analyses found no impact of PD-L1 status on outcomes but linked efficacy to beta-2 microglobulin tumor expression and baseline peripheral blood T cell fitness.
4. Next Steps and IL7 Exploration
Data support advancing the 160 mcg dose into the Phase 3 PRISM-MEL-301 trial evaluating brenetafusp plus nivolumab versus standard nivolumab regimens in first-line advanced melanoma. A separate in vitro poster showed IL7 enhances T cell fitness and ImmTAC-mediated tumor killing, suggesting future combination strategies.
