Initial phase 1b/2 study results of purinostat mesylate (PM) in combination with pomalidomide (POM) and low dexamethasone (DEX) in patients with RRMM.

Abstract

TPS7581 Background: MM remains an incurable disease and resistance mechanisms are emerging. PM is a high selective HDAC I/IIb inhibitor. In phase I study, PM monotherapy had shown good tolerability and efficacy in relapsed/refractory (RR) hematologic malignancies including MM. A phase 1b/2 study is being conducted to further assess the efficacy and safety of PM combined with POM and low DEX (80mg/cycle) in RRMM. Methods: The ongoing phase 1b/2 study includes dose escalation followed by dose expansion. Eligible RRMM had received ≥1 prior line of therapy (LOT) including ≥1 PI and ≥1 IMiD. Cohort A (21D cycle) and Cohort B (28D cycle) of the PM combination regimens are assessed using 3+3 escalation design. Pts in Cohort A receive PM at levels of 4, 6, 8.4, 11.2 and 15mg/m 2 IV on D1,4,8,11; POM 4mg QD on D1-14; DEX 20mg on D1,4,8,11. Pts in Cohort B receive PM at same dose range to Cohort A, on D1,4,15,18; POM 4mg QD on D1-21; DEX 20mg on D1,4,15,18. Pts continue to receive PM until disease progression or unacceptable toxicity. Primary outcomes are DLT and ORR. Secondary outcomes include PFS et al. Results: As of Dec 23, 2025, 27 Pts were recruited including 6 in Cohort A and 21 in Cohort B. The dose had been escalated to 6mg/m 2 and 11.2mg/m 2 in Cohort A and B. Cohort A: Median age was 61.5 years, 66.7% male, 16.7% had prior ASCT. 2 (33.3%) Pts had high risk cytogenetics, including 1q21 duplication (n=1), t (4;14) (n=1) and 1p32 deletion (n=1). 6 Pts were evaluable with median 1 (1-3) prior LOT. The ORR was 50% with 1 sCR and 2 PR along with 1 MR. With a median F/U of 138 days, the median PFS was 151 days (95% CI, 21-NR). Median DOR was NR. The most common ≥ G3 TEAEs were neutropenia (83.3%), lymphocytopenia (83.3%) and thrombocytopenia (100%). No DLT was reported. Cohort B: Median age was 61.0 years, 57.1% male, 19.1% had prior ASCT and 19.1% had extramedullary disease (EMD). 7 (33.3%) Pts had high risk characteristics, including 1q21 duplication (n=7), t (4;14) (n=2) and early relapse after ASCT (n=3). Median prior LOT is 2 (1-5). Among 16 evaluable Pts, the ORR was 37.5% with 1 sCR, 1 CR, 3 VGPR and 1 PR; additional 4 Pts achieved MR. In 7 Pts given the dose of 8.4mg/m 2 , the ORR was 42.9% with 3 VGPR; 3 more Pts achieved MR. With median F/U of 104 days, the median PFS and DOR were NR. The most common ≥ G3 TEAEs were neutropenia (81.0%), lymphocytopenia (61.9%) and thrombocytopenia (38.1%). 1 DLT (G4 neutropenia) was reported. Moreover, in 4 Pts with EMD, 2 achieved objective response. In 4 Pts with super high risk (Double or Triple Hit/early relapse), 1 achieved sCR and 1 achieved VGPR. 1 Pt with prior 5-line therapy including BCMA-ADC had shown VGPR after treatment. Conclusion: PM as a highly selective HDACi in combination with POM and low DEX shown encouraging efficacy and safety in RRMM. Complicated cases with EMD, super high-risk characteristics or heavily pretreatment can benefit from the PM triplet therapy. Clinical trial information: NCT06484829 .