Gotistobart (pH-sensitive anti-CTLA-4) + 177Lu-PSMA-617 logs 67% PSA50 with no DLTs in dose-escalation mCRPC

Gotistobart, a recycling-preserving CTLA-4 antibody that selectively depletes intratumoral Tregs, was paired with standard Lu 177 vipivotide tetraxetan radioligand therapy in the PRESERVE-006 Phase 1 dose-escalation study (NCT05682443). Twenty-four post-ARPI mCRPC patients received Lu 177 Q6W (≤6 doses) plus gotistobart 3 mg/kg Q4W (n=6), 6 mg/kg Q6W (n=5), or 10 mg/kg Q6W (n=6); Lu 177-only served as control (n=7). No dose-limiting toxicities or grade 4/5 TRAEs occurred. Grade 3 colitis emerged in 0% at ≤6 mg/kg and 33% at 10 mg/kg. **Confirmed PSA50 responses were 67% (4/6)**and 50% (3/6)in the 3 mg/kg and 10 mg/kg cohorts versus 17% (1/6) with Lu 177 alone. VISION’s Lu 177 monotherapy benchmark is ~46% PSA50 with 53% grade ≥3 AEs.