The 2026 Congress of the European Society for Medical Oncology (ESMO) is being held in Madrid, Spain. Primary results from the global phase 3 trial of chidamide (HBI-8000, Epidaza®) plus nivolumab in advanced melanoma (Abstract LBA54) were presented by Nikhil I. Khushalani, MD, of Moffitt Cancer Center, in a Proffered Paper session. Additional exploratory studies of chidamide were also presented at the Congress.
Abstract Details
Study Title: Primary Analysis of HBI-8000-303: A Randomized Phase 3 Trial of Nivolumab plus HBI-8000 or Placebo in Advanced Melanoma
Abstract Number: LBA54
Key Findings
Background: Outcome for patients with advanced melanoma has improved significantly with immunotherapy and targeted therapy. In a phase 1b/2 study in anti-PD(L)-1 naïve advanced melanoma, HBI-8000, an oral selective histone deacetylase (HDAC) inhibitor combined with nivolumab (NIVO), achieved an objective response rate (ORR) of 66%. HBI-8000-303 is a global, randomized, double-blind, placebo-controlled phase 3 study of NIVO with HBI-8000/placebo in unresectable or metastatic melanoma not previously treated with PD(L)-1 inhibitors.
Methods: Patients with advanced, non-uveal melanoma with measurable disease, ECOG 0-1, and adequate organ function were randomized to receive oral HBI-8000 30 mg or placebo twice weekly in combination with NIVO 480 mg intravenously every 4 weeks, stratified by tumor PD-L1 expression and serum LDH. The primary endpoint was progression-free survival (PFS) assessed by a Blinded Independent Review Committee. Secondary endpoints were ORR, overall survival, and safety.
Efficacy and Safety: Between July 2021 and April 2024, 404 patients were randomized to HBI-8000 + NIVO (n=203) or placebo + NIVO (n=201). Patient characteristics were well balanced; 33.7% (136/404) with ↑ LDH. Median follow up was 37 months. The median PFS in the HBI-8000 + NIVO arm was 11.7 months (95% CI, 7.3, 21.1), significantly higher than 7.4 months (95% CI, 4.5, 10.1) in the placebo + NIVO arm; hazard ratio 0.73 (96% CI, 0.56 – 0.95, P=0.0141). Confirmed ORR was 41.4% (95% CI, 34.5, 48.5) for HBI-8000 + NIVO, and 32.3% (95% CI, 25.9, 39.3) for placebo + NIVO. The incidence of ≥ Grade 3 treatment related adverse events (TRAEs) was 55% and 18% in the HBI-8000 and placebo arms respectively; 14% and 5% respectively discontinued therapy for any grade TRAEs. Diarrhea, nausea, fatigue, thrombocytopenia, asthenia, and neutropenia were the most common (> 20%) TRAEs for HBI-8000 + NIVO.
Conclusions: HBI-8000 in combination with NIVO results in a significant improvement in PFS compared with NIVO alone in anti-PD(L)-1 naïve advanced melanoma. The toxicity profile is consistent with class effect of HDAC inhibitors and typically reversible. This combination offers a new standard of care for this patient population.
PFS results favored HBI-8000 plus nivolumab across most prespecified subgroups. Overall survival (OS) data remain immature, with follow-up ongoing. Importantly, there was no increase in cases of adrenal insufficiency or hypophysitis, two immune-related adverse events that are often irreversible and have a higher incidence with dual checkpoint inhibition. A manuscript detailing full results of the phase 3 trial of nivolumab with or without HBI-8000 is being submitted for peer review.
Dr. Khushalani, lead investigator for the study, said: “These results show, for the first time, that adding a selective HDAC inhibitor to anti-PD-1 therapy can improve treatment outcomes for patients with advanced melanoma. As a combination therapy that does not rely on dual immune checkpoint inhibition, the immunotoxicity profile is particularly significant given the risk of overlapping toxicities when two checkpoint inhibitors are used together. The fact that HBI-8000 is taken orally and has a predictable side-effect profile may offer advantages over dual checkpoint combinations currently in use.”
Dr. Mireille Gillings, Founder and CEO of HUYABIO, said: “We are delighted to share these exciting results that demonstrate superior efficacy for advanced melanoma patients treated orally with HBI-8000. Immunotherapy has greatly improved clinical outcomes and now there is a new potential standard of care that extends progression free survival, minimizes immunotoxicity, and delivers better quality of life with greater convenience.”
Dr. Xianping Lu, Chairman of Chipscreen Biosciences, said: “This is the first pivotal study to demonstrate, in a multinational, multicenter, double-blind, head-to-head clinical trial, that an HDACi + IO regimen is superior to an immune checkpoint inhibitor, potentially opening a new chapter for the global development of chidamide. Chipscreen Biosciences continues to explore its IO 2.0 strategy based on HDACi + IO. A Phase 3 trial in MSS/pMMR colorectal cancer has completed patient enrollment, with the goal of bringing an immunotherapy option to this large population of patients with ‘cold tumors.’ The next-generation epigenetic immunoconjugate NW001 has received IND approval and may further broaden the therapeutic window compared with combination regimens.”
Beyond melanoma, several combination studies of chidamide in solid tumors were also selected for poster presentation at this year’s Congress, highlighting its broad clinical potential. These studies included “Efficacy and Safety of QL1706 Combined with Chidamide, Nab-Paclitaxel, and Gemcitabine as First-Line Treatment for Metastatic Pancreatic Cancer: A Prospective, Single-Arm Clinical Trial”; “Chidamide Combined with Anlotinib in Patients with Advanced Soft Tissue Sarcoma After Failure of Standard Therapy: A Single-Center, Single-Arm Phase II Trial”; and “Radiotherapy-Induced In Situ Vaccination Combined with Chidamide and PD-1 Antibody for Advanced Soft Tissue Sarcoma: An Exploratory, Single-Center, Single-Arm Trial.”
View source version on businesswire.com: https://www.businesswire.com/news/home/20261026538010/en/
Media gallery
