Unresectable or Metastatic MelanomaPhase 3NCT04674683
Study Comparing Investigational Drug HBI-8000 + Nivolumab vs. Placebo + Nivolumab in Patients With Advanced Melanoma
A Phase 3 study testing HBI-8000 in combination with nivolumab in people with Unresectable or Metastatic Melanoma and Progressive Brain Metastasis, run by HUYABIO International, LLC. at 139 sites in 17 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Unresectable or Metastatic Melanoma, Progressive Brain Metastasis
- What is being tested?
- HBI-8000 in combination with nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 450 participants
- Where
- 139 sitesin 17 countries
- Study dates
- 12 Aug 2021to Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
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- 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.
- Adjuvant or neoadjuvant therapy with PD-1 or PD-L1 inhibitors or anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) is allowed if disease progression/or recurrence had occurred at least 6 months after the last dose of neoadjuvant/adjuvant therapy and prior to receiving the first dose on this study and no clinically significant immune related toxicities leading to treatment discontinuation were observed
- Adjuvant interferon therapy must have been completed > 6 weeks before administration of Study Treatment
- Any prior radiotherapy or minor surgery must be completed at least 2 weeks and 1 week respectively before Day 1 dosing and recovered from all treatment related toxicities
- Screening laboratory results within 14 days prior to randomization:
- Hematology: WBC ≥3000/μL, neutrophils ≥1500/μL, platelets ≥100 × 103/μL, hemoglobin ≥10.0 g/dL independent of transfusion. The use of erythropoietic growth factor to achieve hemoglobin (Hgb) ≥ 10 g/dl is acceptable.
- The CrCL≥ 30 mL/min using Cockcroft-Gault formula.
- AST and ALT ≤3 × ULN, alkaline phosphatase ≤2.5 × ULN unless bone metastases present (patients with documented bone metastases: alkaline phosphatase <5 x ULN), bilirubin ≤ 1.5 × ULN (unless known Gilbert's disease where it must be ≤ 3 × ULN), serum albumin ≥ 3.0 g/dL).
- Negative serum pregnancy test at baseline for women of childbearing potential.
- Females of childbearing potential (non-surgically sterile or premenopausal female capable of becoming pregnant) and all males (due to potential risk of drug exposure through the ejaculate) must agree to use adequate birth control measures from study start, during the study and for 5 months after the last dose of Study Drug. Acceptable methods of birth control in this trial include two highly effective methods of birth control (as determined by the Investigator; one of the methods must be a barrier technique) or abstinence.
- Have the ability to understand and the willingness to sign a written informed consent document, comply with study scheduled treatment, visits and assessments.
Who cannot join
- 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.
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- 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:
- Basal or squamous cell skin cancer
- Superficial bladder cancer
- Carcinoma in situ of cervix or breast
- Incidental prostate cancer
- Non melanomatous skin cancer
- Prostate cancer treated with curative intent with serum prostate specific antigen (PSA) < 2.0 ng/mL
- Patients with medical conditions requiring administration of strong cytochrome P450 (CYP), CYP3A4 Inducers and Inhibitors with no alternative therapy.
- Uncontrolled adrenal insufficiency or active chronic liver disease.
- Has received approved live vaccine/live attenuated vaccines within 30 days of planned Cycle 1 Day 1. Inactivated viral vaccines or vaccines based upon subviral component are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are not allowed. COVID-19 vaccination should be administered at least 7 days before Cycle 1 Day 1.
- Underlying medical conditions that, in the Investigator's opinion, will make the administration of Study Treatment hazardous or obscure the interpretation of toxicity determination or AEs.
- Patients with a history of or active interstitial lung disease (ILD) or non-infectious pneumonitis.
- Patients with prior organ or hematopoietic cell transplant (HCT), including allogeneic HCT.
- Patients with known sensitivity to any of the ingredients of the Study Treatment.
- Patients who received radiation therapy within 14 days of the first dose of the Study Treatment.
- Patients who take drugs that prolong the QT interval or cause torsades de pointes or produce significant ventricular dysrhythmias.
- Patients that are unwilling or unable to comply with procedures required in this protocol.
Trial locations and contacts
139 sites in 17 countries.
139 sites in 17 countries
United States31 sites
AnMed Health
Anderson, South Carolina, 29621
Comprehensive Blood and Cancer Center
Bakersfield, California, 93309
St. Vincent - Frontier Cancer Center
Billings, Montana, 59102
Boca Raton Regional Hospital, Lynn Cancer Institute
Boca Raton, Florida, 33486
St Louis Cancer Care
Bridgeton, Missouri, 63044
Gabrail Cancer Center Research
Canton, Ohio, 44718
Levine Cancer Institute
Charlotte, North Carolina, 28204
St. Elizabeth Healthcare
Edgewood, Kentucky, 41017
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Frederick Memorial Healthcare System
Frederick, Maryland, 21701
Southeastern Medical Oncology Center
Goldsboro, North Carolina, 27534
Goshen Center for Cancer Care
Goshen, Indiana, 46526
Memorial Regional Hospital
Hollywood, Florida, 33021
Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207
AMR Kansas City
Kansas City, Missouri, 64114
UC San Diego Moores Cancer Center
La Jolla, California, 92037
Carolina Blood and Cancer Care Associates
Lancaster, South Carolina, 29720
Baptist Health Lexington
Lexington, Kentucky, 40503
Froedtert Hospital, Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Orlando Health
Orlando, Florida, 32806
Innovative Clinical Research Institute (ICRI)
Pasadena, California, 91105
Ascension Sacred Heart Medical Oncology
Pensacola, Florida, 32504
Thomas Jefferson University Medical Oncology Clinic
Philadelphia, Pennsylvania, 19107
Emad Ibrahim, MD, INC
Redlands, California, 92373
Kaiser Permanente Oncology Research
Riverside, California, 92505
Medisearch Clinical Trials
Saint Joseph, Missouri, 64506
Utah Cancer Specialists
Salt Lake City, Utah, 84106
California Cancer Associates for Research and Excellence, Inc. (cCARE)
San Marcos, California, 92069
Moffitt Cancer Center
Tampa, Florida, 33612
Renovatio Clinical
The Woodlands, Texas, 77380
Toledo Clinic Cancer Center
Toledo, Ohio, 43623
Brazil13 sites
Hopital de Câncer de Barretos-Fundação Pio XII
Barretos, São Paulo, 14784-400
Hospital São Vicente de Paulo
Centro, Rio Grande do Sul, 99010-080
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer,
Curitiba, Paraná, 81520-060
Fundação Doutor Amaral Carvalho
Jaú, São Paulo, 17210-080
Hospital Bruno Born
Lajeado, Rio Grande do Sul, 95900-010
Hospital do Câncer de Londrina
Londrina, Paraná, 86015-520
Centro Gaúcho Integrado de Oncologia, Hematologia
Porto Alegre, Rio Grande do Sul, 90850-170
Ensino e Terapia de Inovação Clίnica AMO-ETICA
Salvador, Estado de Bahia, 41950-610
Hospital de Clίnίcas de Porto Alegre
Santa Cruz do Sul, Rio Grande do Sul, 96810-110
CEPHO-Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André, São Paulo, 09060-650
Oncosite-Centro de Pesquisa Clίnica em Oncologia
São Cristóvão, Rio Grande do Sul, 98700-000
Fundação Faculdade Regional de Medicina de São José do Rio Preto
São José do Rio Preto, São Paulo, 15090-000
Instituto do Cancer do Estado de São Paulo - "Octavio Frias de Oliveira"-ICESP
São Paulo, São Paulo, 01246-000
Germany13 sites
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
Berlin, 10117
Vivantes Klinikum Spandau, Dermatologie und Allergologie
Berlin, 13585
Universitaetsklinikum Koeln, Dermatologie und Venerologie,
Cologne, 50937
Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie
Dresden, 01307
Helios Klinikum Erfurt, Dermatologie und Allergologie
Erfurt, 99089
Universitatsklinikum Essen Klinik fur Dermatologie Studienambulanz
Essen
Universitaetsklinikum Freiburg, Klinik fuer Dermatologie und Venerologie
Freiburg im Breisgau, 79104
Universitaetsklinikum Heidelberg, NCT-Dermatoonkologie
Heidelberg, 69120
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Leipzig, 04103
Universitaetsklinikum Schleswig Holstein - Campus Luebeck
Lübeck, 23538
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz, Hautklinik
Mainz, 55131
Universitaetsklinikum Mannheim, Klinik f. Dermatologie, Venerologie, Allergologle,
Mannheim, 68167
Studienzentrum Dermao-Onkologie, Universitaetsklinikum Tuebingen
Tübingen, 72076
Spain12 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
Catalan Institute of Oncology
Barcelona, 08908
ICO Badalona-Hospital Universitari Germans Trias I Pujol
Barcelona, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona
MD Anderson Cancer Center
Madrid, 28033
Hospital Universitario Fundación Jimenez Diaz
Madrid, 28040
Centro Integral Oncologico Clara Campal
Madrid, 28050
Hospital Universitario Clinico San Carlos
Madrid
Hospital Regional Universitario de Málaga
Málaga, 29010
Hospital Universitario Virgen Macarena
Seville
Hospital Universitario Miguel Servet
Zaragoza
Italy11 sites
IRCCS Giovanni Paolo II Oncologia Medica
Bari, 70124
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
Bologna, 40138
Fondazione IRCCS CA'Granda Ospedale Maggiore Policlinico-Oncologia Medica
Milan, Milano, 20122
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Milano, 20133
Humanitas Istituto Clinico Catanese, U.O. Oncologia Medica
Misterbianco, 95045
Istituto Nazionale Tumori Fondazione G. Pascale, Oncologia Medica e Terapia Innovativa
Naples, 80131
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone - U.O. Oncologia Medica
Palermo, 90127
A.O.S. Maria della Misericordia, Oncologia Medica
Perugia, Perugia, 06132
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00168
A.O.U Senese Policlinico Santa Maria alle Scotte-UOC Immunoterapia Oncologica
Siena, 53100
Policlinico G.B. Rossi-Borgo Roma-Centro Ricerche Cliniche di Verona
Verona, 37134
Australia10 sites
Ballarat Health Services
Ballarat, Victoria
Royal Brisband and Women's Hospital
Brisbane
University of the Sunshine Coast
Buderim, Queensland, 4556
Liverpool Hospital
Liverpool
Affinity Clinical Research
Nedlands
Goulburn Valley Health
Shepparton, Victoria
Icon Cancer Centre Wesley
South Brisbane, Queensland
Tweed Hospital
Tweed Heads
Sydney Adventist Hospital
Wahroonga, New South Wales
Calvary Mater Newcastle
Waratah
France10 sites
CHU de Besançon - Hôpital Jean MINJOZ
Besançon
Hôpital Ambroise Paré
Boulogne-Billancourt
CHU de Dijon, Service de dermatologie
Dijon
CHU Grenoble Alpes
La Tronche
CHRU Lille - Hôpital Claude Huriez, Clinique de Dermatologie
Lille
Hôpital La Timone
Marseille, 13385 Cedex 05
Hôpital Saint-Louis
Paris
Centre Hospitalier Lyon Sud
Pierre-Bénite
CHU de Rouen-Hôpital
Rouen, 76031
Institut Gustave Roussy, Service de Dermatologie
Villejuif
Japan8 sites
National Hospital Organization Osaka National Hospital
Chuo Ku, Osaka, 540-0006
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395
The Cancer Institute Hospital of JFCR
Kōtoku, Tokho, 135-8550
Shinshu University Hospital
Matsumoto, Nagano, 390-8621
Shizuoka Cancer Center
Nagaizumi-cho, Sunto-gun, 411-8777
Niigata Cancer Center Hospital
Niigata, Niigata, 951-8566
Okayama University Hospital
Okayama, Okayama-ken, 700-8558
Osaka Prefectural Hospital Organization Osaka International Cancer Institute
Osaka, Osaka, 541-8567
South Africa7 sites
Excellentis Clinical Trial Consultants
George, Western Cape, 6529
The Medical Oncology Centre of Rosebank
Johannesburg, Gauteng, 2196
Cape Town Oncology Trials Cape Gate Oncology Centre
Kraaifontein, Western Cape, 7570
Wilgers Oncology Centre
Pretoria, Gauteng, 0081
Curo Oncology
Pretoria, Gauteng, 0084
Cancercare Rondebosch Oncology
Rondebosch, Western Cape, 7700
West Rand Oncology Centre Flora Clinic
Roodepoort, Gauteng, 1709
Belgium6 sites
AZ Klina
Brasschaat, 2930
Cliniques Universitaires
Brussels, 1200
AZ Maria Middelares
Ghent, 9000
Jessa Ziekenhuis
Hasselt, 3500
Hospital de la Citadelle
Liège, 4000
Clinique Saint-Pierre
Ottignies, 1340
South Korea6 sites
Chungnam National University Hospital
Daejeon, Jung-gu, 35015
National Cancer Center
Goyang-si, Gyeonggi-do, 10408
Chonnam National University Hwasun Hospital
Hwasun, Jeollanam-do, 58128
Cha University Bundang Medical Center
Seongnam-si, Gyeonggi-do, 13496
Severance Hospital Younsei University Health System,
Seoul, Gyeonggi-do, 03722
Severance Hospital Yonsei University Health System
Seoul, 03722
Czechia3 sites
Fakultni nemocnice Olomoue
Olomouc, 77900
Fakultni nemocnice Ostrava Kozni oddeleni
Ostrava-Poruba, 70852
Fakultni nemocnice Kralovske Vinohrady
Prague, 10034
New Zealand3 sites
Auckland City Hospital
Auckland
Waikato Hospital
Hamilton
Tauranga Hospital
Tauranga, 3112
Austria2 sites
Medical University of Graz Department of Dermatology and Venerology
Graz, 8036
Univ.-Lkinik für Dermatologie, Venerologie und Allergologie
Innsbruck, 6020
United Kingdom2 sites
Nuffield Health Wessex Hospital
Eastleigh, Hampshire, SO53 2DW
Edinburgh Cancer Center Western General Hospital
Edinburgh, EH4 2XU
Puerto Rico1 site
Hospial Oncologico, Puerto Rico Medical Center
Rio Piedras, Puerto Rico, 00935
About this study
Official title: A Multicenter, Randomized, Double-Blind Phase 3 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
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.
Read the detailed description
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab. Randomization of eligible patients will be stratified by PD-L1 expression (positive, ≥1% expression level versus negative, <1% expression level) and LDH (normal versus elevated) in the main study. Adults with new, progressive brain metastasis, or adolescents with or without new progressive brain metastasis will be enrolled in a separate, non-randomized, open-label cohort to receive the combination of HBI-8000 and nivolumab.
In the main study, eligible patients will be randomized within the appropriate stratum at a 1:1 ratio to the Test arm or the Control arm. Study treatment will be initiated within 3 days of randomization.
A treatment cycle consists of 28 days. Patients will be treated with one of the following:
Test arm: HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days
Control arm: Placebo oral BIW + nivolumab IV at specific doses on specific days
The Study Treatment (HBI-8000 or Placebo) is administered approximately 30 minutes after a full meal.
The Study Treatment (HBI-8000 or Placebo) will be administered twice a week on the following days of every 28-day cycle:
- CxW1: Days 1, 4
- CxW2: Days 8, 11
- CxW3: Days 15, 18
- CxW4: Days 22, 25
Study treatment must commence within 3 days after randomization and continue up to 2 years or until disease progression (confirmed), unacceptable toxicity or patient withdrawal of consent.
In addition to Study Treatment, nivolumab is administered at specific doses on specific days as an intravenous infusion over approximately 30 minutes. Nivolumab will be administered on Day 1 of each cycle.
For non-randomized cohort for special population, eligible subjects will receive HBI-8000 30 mg oral BIW and nivolumab IV at specific doses on specific days, under the same schedule as described above. For adolescents weighing < 40 kg, nivolumab will be dosed at specific doses every 4 weeks. Nivolumab will be administered on Day 1 of each cycle.
- Being tested
- HBI-8000 in combination with nivolumab, Placebo in combination with nivolumab
- Keywords
- HBI-8000, nivolumab, melanoma, brain metastasis
- Medical subject headings
- Melanoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HBI-8000 in combination with nivolumabDrug
Also called For HBI-8000: tudicdinostat; For nivolumab: OPDIVO®
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.
Placebo in combination with nivolumabDrug
Also called For nivolumab: OPDIVO®
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.
| Study group | Role | What they receive |
|---|---|---|
| Test Arm | Experimental | HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days Receives: Drug: HBI-8000 in combination with nivolumab |
| Control Arm | Placebo comparator | Placebo oral BIW + nivolumab IV at specific doses on specific days Receives: Drug: Placebo in combination with nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From date of randomization to the earliest date of documented progressive disease (PD), assessed up to 48 months
Secondary outcomes (3)
Objective Response Rate
Objective Response Rate (ORR) defined as the percentage of patients enrolled in each study arm with a best response of Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the blinded independent review committee (BIRC).
Measured: From date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months
Overall Survival
Overall Survival (OS) defined as the time from randomization date to the date of death due to any cause.
Measured: From date of randomization to death due to any cause, assessed up to 48 months
Safety, defined as the incidence rate of AEs
Safety, defined as the incidence rate of AEs. The NCI-CTCAE v5.0 will serve as the reference document for choosing the appropriate terminology to grade the severity of AEs, and to assess the causal relationship and outcomes.
Measured: From date of screening until the end of study, assessed up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start12 Aug 2021
- Primary completionJul 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable or Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 450 participants (actual)
Sponsor and investigators
- Lead sponsor
- HUYABIO International, LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Gloria Lee, MD, PhD, Study director, HUYABIO International, LLC.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04674683
- Sponsor's protocol ID
- HBI-8000-303
- Status last verified
- Sep 2025
- First submitted
- 7 Dec 2020
- Last updated
- 24 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind Phase 3 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
- ClinicalTrials.gov ID
- NCT04674683
- Acronym / sponsor ID
- HBI-8000-303
- Keywords
- HBI-8000, nivolumab, melanoma, brain metastasis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 450 participants (actual)
- Lead sponsor
- HUYABIO International, LLC.Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 12 Aug 2021 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab. Randomization of eligible patients will be stratified by PD-L1 expression (positive, ≥1% expression level versus negative, <1% expression level) and LDH (normal versus elevated) in the main study. Adults with new, progressive brain metastasis, or adolescents with or without new progressive brain metastasis will be enrolled in a separate, non-randomized, open-label cohort to receive the combination of HBI-8000 and nivolumab.
In the main study, eligible patients will be randomized within the appropriate stratum at a 1:1 ratio to the Test arm or the Control arm. Study treatment will be initiated within 3 days of randomization.
A treatment cycle consists of 28 days. Patients will be treated with one of the following:
Test arm: HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days
Control arm: Placebo oral BIW + nivolumab IV at specific doses on specific days
The Study Treatment (HBI-8000 or Placebo) is administered approximately 30 minutes after a full meal.
The Study Treatment (HBI-8000 or Placebo) will be administered twice a week on the following days of every 28-day cycle:
- CxW1: Days 1, 4
- CxW2: Days 8, 11
- CxW3: Days 15, 18
- CxW4: Days 22, 25
Study treatment must commence within 3 days after randomization and continue up to 2 years or until disease progression (confirmed), unacceptable toxicity or patient withdrawal of consent.
In addition to Study Treatment, nivolumab is administered at specific doses on specific days as an intravenous infusion over approximately 30 minutes. Nivolumab will be administered on Day 1 of each cycle.
For non-randomized cohort for special population, eligible subjects will receive HBI-8000 30 mg oral BIW and nivolumab IV at specific doses on specific days, under the same schedule as described above. For adolescents weighing < 40 kg, nivolumab will be dosed at specific doses every 4 weeks. Nivolumab will be administered on Day 1 of each cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab.
| Arm | Type | Receives |
|---|---|---|
| Test Arm | Experimental | Drug: HBI-8000 in combination with nivolumabHBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days |
| Control Arm | Placebo comparator | Drug: Placebo in combination with nivolumabPlacebo oral BIW + nivolumab IV at specific doses on specific days |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- 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:
- 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.
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HBI-8000 in combination with nivolumabAlso: For HBI-8000: tudicdinostat; For nivolumab: OPDIVO®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. | Drug | Test Arm |
| Placebo in combination with nivolumabAlso: For nivolumab: OPDIVO®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. | Drug | Control Arm |
Primary outcome
Primary Outcome
Time frame: From date of randomization to the earliest date of documented progressive disease (PD), assessed up to 48 months
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.
3 secondary outcomes
Objective Response Rate
Time frame: From date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months
Overall Survival
Time frame: From date of randomization to death due to any cause, assessed up to 48 months
Safety, defined as the incidence rate of AEs
Time frame: From date of screening until the end of study, assessed up to 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2025.
- MedlinePlus Genetics related topics: MelanomaLink provided by the sponsor.
- MedlinePlus related topics: MelanomaLink provided by the sponsor.
- Drug Information available for: NivolumabLink provided by the sponsor.
- Genetic and Rare Diseases Information Center resources: Neuroendocrine Tumor NeuroepitheliomaLink provided by the sponsor.
- U.S. FDA ResourcesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gloria Lee, MD, PhD study director
HUYABIO International, LLC.
139 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HBI-8000 in combination with nivolumab in people with Unresectable or Metastatic Melanoma and Progressive Brain Metastasis, run by HUYABIO International, LLC. at 139 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 139 sites in United States, Brazil, Germany, Spain, Italy and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Outcome (time frame: From date of randomization to the earliest date of documented progressive disease (PD), assessed up to 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2025.