Muzastotug (ADG126) masked anti-CTLA-4 + atezolizumab/bevacizumab lifts ORR to 50% in 1L uHCC (tiny n)

Muzastotug (ADG126) is a protease-activated, Treg-depleting anti-CTLA-4 IgG1 designed for tumor-local activation (reported ~10× higher ADCC than ipilimumab) and was added to atezolizumab (PD-L1) + bevacizumab (VEGF) in the Phase 1b/2 MORPHEUS-Liver platform (NCT04524871) for previously untreated unresectable locally advanced/metastatic HCC. As of July 11, 2025, ORR was 50% (3/6) with ADG126+Atezo+Bev vs 17.5% (7/40) with Atezo+Bev; DCR was 83% vs 53%, and median DOR was not reached in the triplet responders (>18.1, >13.8, >4 months), with “longer PFS/OS” but no medians/HRs provided in the abstract. Grade ≥3 TRAEs were similar (50% vs 45%) and no fatal AEs occurred; triplet-arm grade ≥3 events listed included hypertension/proteinuria, infusion reaction, and AST increase/pyrexia, with no ADG126 dose reductions; two patients discontinued Bev yet continued ADG126+Atezo (one >630 days)—a practical angle given Bev’s bleeding/proteinuria risk, but the efficacy benchmark remains the established 1L SOC Atezo+Bev from IMbrave150 (median PFS ~6.8 months; ORR commonly reported ~27–30% per RECIST 1.1, depending on assessment).