Resminostat in patients with relapsed or refractory Hodgkin lymphoma: results of the phase II SAPHIRE study

Abstract

This open-label, single-arm phase II study examined efficacy, safety, pharmacokinetics, and biomarkers of histone deacetylase (HDAC) inhibitor resminostat in patients with relapsed or refractory Hodgkin lymphoma. Thirty-seven heavily pretreated patients received 600 (19 patients) or 800 mg (18 patients) oral resminostat daily for the initial 5 days of 14-day treatment cycles. Objective response rate (ORR) (primary) was 34% reaching disease control in 54% patients. Most patients (69%) showed reduced tumor size and reduced [F]-FDG uptake in target lesions (71%). Median progression-free survival (PFS) was 2.3 months (95%CI [1.3; 3.3]) and median overall survival (OS) was 12.5 months (95%CI [9.6; 18.6]). Patients who responded or stabilized under resminostat had a 10-month longer OS than patients who progressed. Efficacy assessment, pharmacodynamics, and exploratory biomarker results followed plasma levels, showed target engagement and epigenetic modulations. Common drug-related adverse events (AEs) were nausea, vomiting, anemia, thrombocytopenia, and fatigue, mainly grade 1 or 2.

<p>Safety and Efficacy of Brentuximab Vedotin in the Treatment of Classic Hodgkin Lymphoma</p>

“…Recent advances in basic research have revealed molecular pathogenesis of cHL (Figure 6) 101,102 leading to the clinical development of several targeted small molecules (Table 6). [103][104][105][106][107][108][109][110][111][112] However, the development of these small molecules fell out of favor because of their moderate efficacy with singleagent use. Currently, the combination of BV and/or immune checkpoint inhibitors with small molecules is being tested in early phase trials.…”

The changing therapeutic landscape, burden of disease, and unmet needs in patients with cutaneous T‐cell lymphoma

“…Previously tested in Phase I or II studies in patients with hepatocellular carcinoma, Hodgkin lymphoma, biliary tract and pancreatic cancer, and non‐small cell lung cancer 86,92,93,95 …”

Optimizing outcomes in relapsed/refractory Hodgkin lymphoma: a review of current and forthcoming therapeutic strategies

“…The 110 mg dose level provided slightly better ORR, but was not well tolerated, with two deaths potentially related to treatment, while the results of entinostat and resminostat were less encouraging. [195][196][197] JAK inhibitors could be active in HL through the blockade of the JAK-STAT pathway. Unfortunately, the clinical results of pacritinib and ruxolitinib were heterogenous and rather disappointing (Table 3).…”

“…Several novel agents had shown promising results, but their development was delayed or stopped with the appearance of the impressive results obtained with BV and checkpoint inhibitors. The potential role of such targeted agents in rr-cHL, including mTOR inhibitors, lenalidomide, histone deacetylase inhibitors (HDACi), and JAK inhibitors, as well as inhibitors of the B-cell receptor (BCR) pathway, 189–210 and details of major clinical trials of these agents are summarized in Table 3.…”

“…The 110 mg dose level provided slightly better ORR, but was not well tolerated, with two deaths potentially related to treatment, while the results of entinostat and resminostat were less encouraging. 195–197…”