High HDAC I/IIb selective inhibitor purinostat mesylate in relapsed and refractory diffuse large B-cell lymphoma: A single agent phase IIb study.

Abstract

7047 Background: Relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) has a poor prognosis. Purinostat Mesylate (PM) is a high selective HDAC I/IIb inhibitor. PM has demonstrated its safety and efficacy in r/r DLBCL in previous studies. Based on results of phase IIa, 11.2mg/m 2 was chosen to be the RP2D. The efficacy and safety of PM monotherapy in r/r DLBCL patients are evaluated in phase IIb study (NCT05563844). Methods: This multicenter, single-arm, phase IIb study is conducted in 37 sites in China. Key eligibilities include r/r DLBCL 2~5 lines; prior therapies include anti-CD20 monoclonal antibody and anthracycline-based chemotherapy; ECOG≤2. The IIb study plans to enroll 90 patients to receive IV of PM at 11.2mg/m 2 on day 1, 4, 8, 11 of 21-day cycle. Patients continue to receive PM until disease progression or unacceptable toxicity. Primary outcome is ORR. Secondary outcomes include PFS, OS and safety. Results: As of2025.1.18, 44 r/r DLBCL patients had been enrolled (median age 62.5 years, 45.5% female) with a median of 2 lines of prior therapy. 43 patients have at least one response evaluation. After a median follow-up of 6.0 months, the ORR is 60.5%（26/43）with 9 complete response (CR) and 17 partial response (PR). Most response (19/26) occurred at early cycle with median TTR of 1.3 months (95% CI, 1.25-2.00), and the mDOR is 8.6 months (95% CI, 4.24- NR). Among 26 patients with response, 16 patients remain on treatment and the longest treatment has lasted for 22 cycles (still CR at cycle 21). The mPFS is 6.2 months (95% CI, 3.22-NR) and the mOS is immature. In subgroup analysis, 16 double-expressor DLBCL patients obtained 56.3% (9/16) ORR and 32 patients with TP53 mutation by NGS/FISH test achieved 62.5% (20/32) ORR. The most common grade ≥3 treatment emergent adverse events include thrombocytopenia (81.8%), neutropenia (79.5%), leukocytopenia (47.7%), lymphocytopenia (27.3%), hypokalemia (11.4%), anemia (9.1%) and hypertriglyceridemia (9.1%). No PM-related death was reported. Conclusion: This ongoing study showed 11.2mg/m 2 PM in 21-day-cycle achieved remarkable efficacy in r/r DLBCL and acceptable safety profile. The strategy for pivotal study of PM in r/r DLBCL is discussed with NMPA. Clinical trial information: NCT05563844 .