NCT04674683

Brief Summary

This is a clinical study to compare the efficacy and safety of HBI-8000 combined with nivolumab to Placebo combined with nivolumab in patients with unresectable or metastatic melanoma. A separate open-label cohort of adults with new, progressive brain metastasis or adolescents with or without new progressive brain metastasis receive HBI-8000 combined with nivolumab.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
450

participants targeted

Target at P50-P75 for phase_3

Timeline
7mo left

Started Aug 2021

Longer than P75 for phase_3

Geographic Reach
16 countries

137 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress89%
Aug 2021Dec 2026

First Submitted

Initial submission to the registry

December 7, 2020

Completed
12 days until next milestone

First Posted

Study publicly available on registry

December 19, 2020

Completed
8 months until next milestone

Study Start

First participant enrolled

August 12, 2021

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2026

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2026

Last Updated

September 24, 2025

Status Verified

September 1, 2025

Enrollment Period

4.9 years

First QC Date

December 7, 2020

Last Update Submit

September 18, 2025

Conditions

Keywords

HBI-8000nivolumabmelanomabrain metastasis

Outcome Measures

Primary Outcomes (1)

  • Primary Outcome

    Progression-free Survival (PFS) defined as the time (in days) from the date of randomization to the first date of documented disease progression as determined by BIRC, or the date of death due to any cause, whichever occurs first.

    From date of randomization to the earliest date of documented progressive disease (PD), assessed up to 48 months

Secondary Outcomes (3)

  • Objective Response Rate

    From date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months

  • Overall Survival

    From date of randomization to death due to any cause, assessed up to 48 months

  • Safety, defined as the incidence rate of AEs

    From date of screening until the end of study, assessed up to 48 months

Other Outcomes (4)

  • Duration of Response

    Assessed up to 48 months

  • Disease Control Rate

    Assessed up to 48 months

  • Time to Response

    Assessed up to 48 months

  • +1 more other outcomes

Study Arms (2)

Test Arm

EXPERIMENTAL

HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days

Drug: HBI-8000 in combination with nivolumab

Control Arm

PLACEBO COMPARATOR

Placebo oral BIW + nivolumab IV at specific doses on specific days

Drug: Placebo in combination with nivolumab

Interventions

Patients will take 30 mg of HBI-8000 orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV will be administered by intravenous infusion at specific doses on specific days in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice. In adolescent patients with body weight \< 40 kg, nivolumab will be dosed at specific doses on specific days.

Also known as: For HBI-8000: tudicdinostat; For nivolumab: OPDIVO®
Test Arm

Patients will take 30 mg of Placebo orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV at specific doses will be administered by intravenous infusion in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice.

Also known as: For nivolumab: OPDIVO®
Control Arm

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Histopathologically confirmed diagnosis of non-uveal, Stage III (unresectable), or Stage IV (metastatic) melanoma according to AJCC staging system (8th edition).
  • Known BRAF V600 mutation status or consent to BRAF V600 mutation testing before randomization.
  • Tumor tissue available for PD-L1 testing at central lab or local laboratory; results must be obtained prior to randomization. In the event when archived tumor tissue is not available, new tumor biopsy or historical PD-L1 test results may be used for randomization, however tumor tissue, either taken previously or newly acquired, must be provided for central biomarker confirmation for final data analyses.
  • PD-L1 expression level is required for randomization. In order to be randomized, a patient must be classified as PD-L1 positive or PD-L1 negative according to the following criteria:
  • PD-L1 positive (≥ 1% tumor cell membrane staining in a minimum of a hundred evaluable tumor cells) vs
  • PD-L1 negative (\< 1% tumor cell membrane staining in a minimum of a hundred evaluable tumor cells).
  • Note: If an insufficient amount of tumor tissue is available prior to the start of the screening phase, patients must consent to allow the acquisition of additional tumor tissue for performance of biomarker analyses.
  • Males or females 12 years of age or older.
  • ECOG performance status ≤1 for age ≥18 years, Lansky performance status ≥80% for age 12 to 17 years.
  • At least one measurable lesion defined by RECIST 1.1 criteria, (separate from the lesion to be used for tumor tissue collection) not counting brain metastasis with:
  • Longest diameter ≥10 mm by CT (when slice thickness is ≤5 mm); or ≥ 2× slice thickness (when slice thickness is \>5 mm)
  • Pathologically enlarged lymph node: ≥15 mm in short axis by CT (when slice thickness is ≤5 mm)
  • Clinical: ≥10 mm (that can be accurately measured with calipers).
  • Have not received anti-PD-1, anti-PD-L1 or other systemic therapy for unresectable or metastatic melanoma, except for the following, provided that the patient has recovered from all treatment-related toxicities:
  • BRAF mutation targeting therapy \> 4 weeks before administration of Study Treatment.
  • +10 more criteria

You may not qualify if:

  • History of ≥ Grade 3 hypersensitivity reactions to monoclonal antibodies.
  • Previous treatment with a PD-1, PD-L1, PD-L2, CTLA-4 inhibitor, or any other agents targeting T-cell co-stimulation or immune checkpoint pathways for unresectable or metastatic melanoma.
  • Recipient of solid organ transplant.
  • History of a cardiovascular illness including: congestive heart failure (New York Heart Association Grade III or IV); unstable angina or myocardial infarction within the previous 6 months prior to first dose of Study Treatment; or symptomatic cardiac arrhythmia despite medical management. QT interval corrected by heart rate using QTcF \>450 ms in males or \>470 ms in females, or congenital long QT syndrome.
  • Uncontrolled hypertension, systolic blood pressure (SBP) \>160 mmHg or diastolic blood pressure (DBP) \>100 mmHg.
  • Patients with new, active, or progressive brain metastases or leptomeningeal disease with except when considered for a separate special open-label cohort.
  • History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer, or bowel resection that affects absorption of orally administered drugs.
  • Active, known, or suspected autoimmune disease, except for Type I diabetes mellitus, hypothyroidism requiring only hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic therapy.
  • Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
  • Known history of testing positive for HIV, known AIDS.
  • Hepatitis B surface antigen positive or hepatitis C antibody positive. Further investigation per institutional practices may be performed to exclude active infection.
  • Patients with a condition requiring chronic systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days before administration of Study Treatment. Inhaled or topical steroids, or adrenal replacement dose of corticosteroids at dose ≤ 10 mg/day prednisone equivalent are permitted.
  • Use of another investigational agent (drug or vaccine not marketed for any indication) within 28 days or before administration of Study Treatment. If the investigational agent is a monoclonal antibody then within 3 months before administration of Study Treatment
  • Pregnant or breast-feeding women.
  • Have a history of any other malignancy unless in remission for 2 years or locally curable cancers that have been treated with curative intent with no evidence of recurrence, such as:
  • +16 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (139)

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92037, United States

Location

Innovative Clinical Research Institute (ICRI)

Pasadena, California, 91105, United States

Location

Emad Ibrahim, MD, INC

Redlands, California, 92373, United States

Location

Kaiser Permanente Oncology Research

Riverside, California, 92505, United States

Location

California Cancer Associates for Research and Excellence, Inc. (cCARE)

San Marcos, California, 92069, United States

Location

Boca Raton Regional Hospital, Lynn Cancer Institute

Boca Raton, Florida, 33486, United States

Location

Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Ascension Sacred Heart Medical Oncology

Pensacola, Florida, 32504, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

St. Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

Frederick Memorial Healthcare System

Frederick, Maryland, 21701, United States

Location

St Louis Cancer Care

Bridgeton, Missouri, 63044, United States

Location

AMR Kansas City

Kansas City, Missouri, 64114, United States

Location

Medisearch Clinical Trials

Saint Joseph, Missouri, 64506, United States

Location

St. Vincent - Frontier Cancer Center

Billings, Montana, 59102, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Southeastern Medical Oncology Center

Goldsboro, North Carolina, 27534, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

Location

Thomas Jefferson University Medical Oncology Clinic

Philadelphia, Pennsylvania, 19107, United States

Location

AnMed Health

Anderson, South Carolina, 29621, United States

Location

Carolina Blood and Cancer Care Associates

Lancaster, South Carolina, 29720, United States

Location

Renovatio Clinical

The Woodlands, Texas, 77380, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Froedtert Hospital, Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Location

University of the Sunshine Coast

Buderim, Queensland, 4556, Australia

Location

Icon Cancer Centre Wesley

South Brisbane, Queensland, Australia

Location

Ballarat Health Services

Ballarat, Victoria, Australia

Location

Goulburn Valley Health

Shepparton, Victoria, Australia

Location

Royal Brisband and Women's Hospital

Brisbane, Australia

Location

Liverpool Hospital

Liverpool, Australia

Location

Affinity Clinical Research

Nedlands, Australia

Location

Tweed Hospital

Tweed Heads, Australia

Location

Calvary Mater Newcastle

Waratah, Australia

Location

Medical University of Graz Department of Dermatology and Venerology

Graz, 8036, Austria

Location

Univ.-Lkinik für Dermatologie, Venerologie und Allergologie

Innsbruck, 6020, Austria

Location

AZ Klina

Brasschaat, 2930, Belgium

Location

Cliniques Universitaires

Brussels, 1200, Belgium

Location

AZ Maria Middelares

Ghent, 9000, Belgium

Location

Jessa Ziekenhuis

Hasselt, 3500, Belgium

Location

Hospital de la Citadelle

Liège, 4000, Belgium

Location

Clinique Saint-Pierre

Ottignies, 1340, Belgium

Location

Ensino e Terapia de Inovação Clίnica AMO-ETICA

Salvador, Estado de Bahia, 41950-610, Brazil

Location

Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer,

Curitiba, Paraná, 81520-060, Brazil

Location

Hospital do Câncer de Londrina

Londrina, Paraná, 86015-520, Brazil

Location

Hospital São Vicente de Paulo

Centro, Rio Grande do Sul, 99010-080, Brazil

Location

Hospital Bruno Born

Lajeado, Rio Grande do Sul, 95900-010, Brazil

Location

Centro Gaúcho Integrado de Oncologia, Hematologia

Porto Alegre, Rio Grande do Sul, 90850-170, Brazil

Location

Hospital de Clίnίcas de Porto Alegre

Santa Cruz do Sul, Rio Grande do Sul, 96810-110, Brazil

Location

Oncosite-Centro de Pesquisa Clίnica em Oncologia

São Cristóvão, Rio Grande do Sul, 98700-000, Brazil

Location

Hopital de Câncer de Barretos-Fundação Pio XII

Barretos, São Paulo, 14784-400, Brazil

Location

Fundação Doutor Amaral Carvalho

Jaú, São Paulo, 17210-080, Brazil

Location

CEPHO-Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, São Paulo, 09060-650, Brazil

Location

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Instituto do Cancer do Estado de São Paulo - "Octavio Frias de Oliveira"-ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Fakultni nemocnice Olomoue

Olomouc, 77900, Czechia

Location

Fakultni nemocnice Ostrava Kozni oddeleni

Ostrava-Poruba, 70852, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 10034, Czechia

Location

CHU de Besançon - Hôpital Jean MINJOZ

Besançon, France

Location

Hôpital Ambroise Paré

Boulogne-Billancourt, France

Location

CHU de Dijon, Service de dermatologie

Dijon, France

Location

CHU Grenoble Alpes

La Tronche, France

Location

CHRU Lille - Hôpital Claude Huriez, Clinique de Dermatologie

Lille, France

Location

Hôpital La Timone

Marseille, 13385 Cedex 05, France

Location

Hôpital Saint-Louis

Paris, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

CHU de Rouen-Hôpital

Rouen, 76031, France

Location

Institut Gustave Roussy, Service de Dermatologie

Villejuif, France

Location

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, 10117, Germany

Location

Vivantes Klinikum Spandau, Dermatologie und Allergologie

Berlin, 13585, Germany

Location

Universitaetsklinikum Koeln, Dermatologie und Venerologie,

Cologne, 50937, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie

Dresden, 01307, Germany

Location

Helios Klinikum Erfurt, Dermatologie und Allergologie

Erfurt, 99089, Germany

Location

Universitatsklinikum Essen Klinik fur Dermatologie Studienambulanz

Essen, Germany

Location

Universitaetsklinikum Freiburg, Klinik fuer Dermatologie und Venerologie

Freiburg im Breisgau, 79104, Germany

Location

Universitaetsklinikum Heidelberg, NCT-Dermatoonkologie

Heidelberg, 69120, Germany

Location

Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie

Leipzig, 04103, Germany

Location

Universitaetsklinikum Schleswig Holstein - Campus Luebeck

Lübeck, 23538, Germany

Location

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz, Hautklinik

Mainz, 55131, Germany

Location

Universitaetsklinikum Mannheim, Klinik f. Dermatologie, Venerologie, Allergologle,

Mannheim, 68167, Germany

Location

Studienzentrum Dermao-Onkologie, Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Fondazione IRCCS CA'Granda Ospedale Maggiore Policlinico-Oncologia Medica

Milan, Milano, 20122, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Milano, 20133, Italy

Location

A.O.S. Maria della Misericordia, Oncologia Medica

Perugia, Perugia, 06132, Italy

Location

IRCCS Giovanni Paolo II Oncologia Medica

Bari, 70124, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, 40138, Italy

Location

Humanitas Istituto Clinico Catanese, U.O. Oncologia Medica

Misterbianco, 95045, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale, Oncologia Medica e Terapia Innovativa

Napoli, 80131, Italy

Location

Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone - U.O. Oncologia Medica

Palermo, 90127, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

A.O.U Senese Policlinico Santa Maria alle Scotte-UOC Immunoterapia Oncologica

Siena, 53100, Italy

Location

Policlinico G.B. Rossi-Borgo Roma-Centro Ricerche Cliniche di Verona

Verona, 37134, Italy

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, 811-1395, Japan

Location

Shinshu University Hospital

Matsumoto, Nagano, 390-8621, Japan

Location

Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

National Hospital Organization Osaka National Hospital

Chuo Ku, Osaka, 540-0006, Japan

Location

Osaka Prefectural Hospital Organization Osaka International Cancer Institute

Osaka, Osaka, 541-8567, Japan

Location

Shizuoka Cancer Center

Nagaizumi-cho, Sunto-gun, 411-8777, Japan

Location

The Cancer Institute Hospital of JFCR

Kōtoku, Tokho, 135-8550, Japan

Location

Auckland City Hospital

Auckland, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

Tauranga Hospital

Tauranga, 3112, New Zealand

Location

Hospial Oncologico, Puerto Rico Medical Center

Rio Piedras, Puerto Rico, 00935, Puerto Rico

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

The Medical Oncology Centre of Rosebank

Johannesburg, Gauteng, 2196, South Africa

Location

Wilgers Oncology Centre

Pretoria, Gauteng, 0081, South Africa

Location

Curo Oncology

Pretoria, Gauteng, 0084, South Africa

Location

West Rand Oncology Centre Flora Clinic

Roodepoort, Gauteng, 1709, South Africa

Location

Excellentis Clinical Trial Consultants

George, Western Cape, 6529, South Africa

Location

Cape Town Oncology Trials Cape Gate Oncology Centre

Kraaifontein, Western Cape, 7570, South Africa

Location

Cancercare Rondebosch Oncology

Rondebosch, Western Cape, 7700, South Africa

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Cha University Bundang Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Severance Hospital Younsei University Health System,

Seoul, Gyeonggi-do, 03722, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

Location

Chungnam National University Hospital

Daejeon, Jung-gu, 35015, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Catalan Institute of Oncology

Barcelona, 08908, Spain

Location

ICO Badalona-Hospital Universitari Germans Trias I Pujol

Barcelona, 08916, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario Fundación Jimenez Diaz

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Nuffield Health Wessex Hospital

Eastleigh, Hampshire, SO53 2DW, United Kingdom

Location

Edinburgh Cancer Center Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Related Links

MeSH Terms

Conditions

MelanomaBrain Neoplasms

Interventions

HBI-8000Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue DiseasesCentral Nervous System NeoplasmsNervous System NeoplasmsBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Gloria Lee, MD, PhD

    HUYABIO International, LLC.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
All Eligible patients will be randomized within the appropriate stratum at a 1:1 ratio to the Test arm or the Control arm, with the exception of Cohort for special population.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: This is a double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 7, 2020

First Posted

December 19, 2020

Study Start

August 12, 2021

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

December 1, 2026

Last Updated

September 24, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations