42TiP - 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

Background

HBI-8000 also known as tucidinostat is an orally bioavailable, low-nanomolar 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, <1% expression level) and lactate dehydrogenase (LDH) level (normal versus elevated). Patients will be treated with one of the following: Test arm: HBI-8000 30 mg oral twice a week (BIW) + nivolumab 480 mg intravenous (IV) every 4 weeks (Q4W) Control arm: Placebo oral BIW + nivolumab 480 mg IV Q4W The study began enrolling patients in August 2021 and is ongoing in 13 countries including Australia, Austria, Belgium, Brazil, Czech Republic, France, Germany, Italy, New Zealand, South Africa, Spain, United Kingdom and United States of America.

Clinical trial identification

NCT04674683.

Legal entity responsible for the study

HUYA Bioscience International.

Funding

HUYA Bioscience International.

Disclosure

F. Shojaei, J. Ning, L. Aiyer, M. Gillings, F. Kabbinavar: Financial Interests, Personal, Full or part-time Employment: HUYA Bioscience International. All other authors have declared no conflicts of interest.