Haihe’s HH2853 (EZH1/2 dual) achieves 31% ORR, 16-mo mPFS in epithelioid sarcoma

HH2853 is an oral dual EZH1/2 histone-methyltransferase (PRC2) inhibitor; in an open-label, global Phase I dose-escalation/expansion (NCT04390737) across refractory solid tumors and NHL (n=61; 57 evaluable), seven BID dose levels (50–1000 mg, 28-day cycles) were tested, 400/600 mg were expanded, and RP2D=400 mg BID. Overall ORR was 27.9% (4 CR, 13 PR); in epithelioid sarcoma (ES) ORR was 31.3% (95% CI 16.0–50.0) with mPFS 16.0 mo, contributing 58.8% of all responses. TRAEs occurred in 95.1% (grade≥3 anemia 11.5%, diarrhea 8.2%, thrombocytopenia 6.6%); 2 DLTs at 800 mg, no treatment-related deaths; compared with tazemetostat (EZH2-only; ORR 15%, mPFS 5.5 mo) and typical anthracycline/gemcitabine outcomes (ORR 22–27%, mPFS 4–6 mo), the ES signal appears stronger but needs randomized validation.