A multicenter, randomized, double-blind phase III study of HBI-8000 combined with nivolumab versus placebo with nivolumab in patients with unresectable or metastatic melanoma not previously treated with PD-1 or PD-L1 inhibitors.

Abstract

Background: HBI-8000 also known as tucidinostat is an orally bioavailable, lownanomolar inhibitor of cancer-associated histone deacetylase enzymes. HBI-8000 is a histone deacetylase inhibitor (HDACi), and as an epigenetic regulator modulating the gene expression, without changing the DNA sequence. HBI-8000 is being developed as a monotherapy for the treatment of hematological malignancies and in combinations for the treatment of solid tumors such as melanoma, breast, kidney, and lung cancers. Trial design: This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab in patients with unresectable or metastatic melanoma not previously treated with program cell death protein 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) Inhibitors (NCT04674683). Approximately 480 patients (including approximately 30 patients in special open-label, non-randomized cohort who are either adolescents 12 years of age or patients with new, progressive brain metastasis) with metastatic or unresectable melanoma who have not received anti-PD-1 or anti-PD-L1 for their disease will be enrolled. Eligible patients will be randomized within appropriate stratum at a ratio of 1:1 stratified by PD-L1 expression (positive, 1% expression level versus negative,