Study Comparing Investigational Drug HBI-8000 Combined With Nivolumab vs. Nivolumab in Patients With Advanced Melanoma

July 25, 2023 updated by: HUYABIO International, LLC.

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 phase 3 study to compare the efficacy and safety of HBI-8000 or Placebo combined with nivolumab on patients with unresectable or metastatic melanoma and eligible patients who are not adolescents or patients with new, progressive brain metastasis will be stratified by PD-L1 expression and LDH level.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

480

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Brisbane, Australia
      • Liverpool, Australia
        • Recruiting
        • Liverpool Hospital
        • Contact:
          • Bavanthi Balkrishnar
          • Phone Number: 02 8738 9744
      • Nedlands, Australia
      • Tweed Heads, Australia
        • Recruiting
        • Tweed Hospital
      • Waratah, Australia
    • New South Wales
      • Wahroonga, New South Wales, Australia
    • Queensland
      • Buderim, Queensland, Australia, 4556
        • Recruiting
        • University of the Sunshine Coast
        • Contact:
        • Principal Investigator:
          • Hong Shue, M.D.
      • Sippy Downs, Queensland, Australia, 4556
        • Recruiting
        • University of the Sunshine
      • South Brisbane, Queensland, Australia
        • Recruiting
        • Icon Cancer Centre Wesley
        • Contact:
        • Principal Investigator:
          • Agnieszka Malczewski, M.D.
    • Victoria
      • Ballarat, Victoria, Australia
        • Recruiting
        • Ballarat Health Services
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sharad Sharma, MD
      • Shepparton, Victoria, Australia
  • Austria
      • Graz, Austria, 8036
        • Recruiting
        • Medical University of Graz Department of Dermatology and Venerology
      • Innsbruck, Austria, 6020
        • Recruiting
        • Univ.-Lkinik für Dermatologie, Venerologie und Allergologie
  • Belgium
      • Brasschaat, Belgium, 2930
        • Recruiting
        • AZ Klina
      • Brussels, Belgium, 1200
        • Recruiting
        • Cliniques Universitaires
      • Ghent, Belgium, 9000
        • Recruiting
        • AZ Maria Middelares
      • Hasselt, Belgium
        • Recruiting
        • Jessa ziekenhuis
      • Hasselt, Belgium, 3500
        • Recruiting
        • Jessa ziekenhuis
      • Liège, Belgium, 4000
        • Recruiting
        • Hospital de la Citadelle
      • Ottignies, Belgium, 1340
        • Recruiting
        • Clinique Saint-Pierre
  • Brazil
      • São Paulo, Brazil, 01246-000
        • Recruiting
        • Instituto do Cancer do Estado de São Paulo - "Octavio Frias de Oliveira"-ICESP
    • Bahia
      • Salvador, Bahia, Brazil, 41950-610
        • Recruiting
        • Ensino e Terapia de Inovação Clίnica AMO-ETICA
    • Paraná
      • Curitiba, Paraná, Brazil, 81520-060
        • Recruiting
        • Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer,
      • Londrina, Paraná, Brazil, 86015-520
        • Recruiting
        • Hospital do Cancer de Londrina
    • Rio Grande Do Sul
      • Centro, Rio Grande Do Sul, Brazil, 99010-080
        • Recruiting
        • Hospital Sao Vicente de Paulo
      • Lajeado, Rio Grande Do Sul, Brazil, 95900-010
        • Recruiting
        • Hospital Bruno Born
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90850-170
        • Recruiting
        • Centro Gaúcho Integrado de Oncologia, Hematologia
      • Santa Cruz Do Sul, Rio Grande Do Sul, Brazil, 96810-110
        • Recruiting
        • Hospital de Clίnίcas de Porto Alegre
      • São Cristóvão, Rio Grande Do Sul, Brazil, 98700-000
        • Recruiting
        • Oncosite-Centro de Pesquisa Clίnica em Oncologia
    • Sao Paulo
      • Barretos, Sao Paulo, Brazil, 14784-400
        • Recruiting
        • Hopital de Câncer de Barretos-Fundação Pio XII
    • São Paulo
      • Jaú, São Paulo, Brazil, 17210-080
        • Recruiting
        • Fundação Doutor Amaral Carvalho
      • São José Do Rio Preto, São Paulo, Brazil, 15090-000
        • Recruiting
        • Fundação Faculdade Regional de Medicina de São José do Rio Preto
    • São Paulo,
      • Santo André, São Paulo,, Brazil, 09060-650
        • Recruiting
        • CEPHO-Centro de Estudos e Pesquisas de Hematologia e Oncologia
  • Czechia
      • Olomouc, Czechia, 77900
        • Recruiting
        • Fakultni nemocnice Olomoue
      • Ostrava-Poruba, Czechia, 70852
        • Recruiting
        • Fakultni nemocnice Ostrava Kozni oddeleni
      • Prague, Czechia, 10034
        • Recruiting
        • Fakultní Nemocnice Královské Vinohrady
  • France
      • Besançon, France
        • Recruiting
        • CHU de Besançon - Hôpital Jean Minjoz
      • Boulogne-Billancourt, France
        • Recruiting
        • Hôpital Ambroise Paré
      • Dijon, France
        • Recruiting
        • CHU de Dijon, Service de dermatologie
      • La Tronche, France
        • Recruiting
        • CHU Grenoble Alpes
      • Lille, France
        • Recruiting
        • CHRU Lille - Hôpital Claude Huriez, Clinique de Dermatologie
      • Marseille, France, 13385 Cedex 05
        • Recruiting
        • Hôpital La Timone
      • Paris, France
        • Recruiting
        • Hôpital Saint-Louis
      • Pierre-Bénite, France
        • Recruiting
        • Centre Hospitalier Lyon Sud
      • Rouen, France, 76031
        • Recruiting
        • CHU de Rouen-Hôpital
      • Villejuif, France
        • Recruiting
        • Institut Gustave Roussy, Service de Dermatologie
  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
      • Berlin, Germany, 13585
        • Recruiting
        • Vivantes Klinikum Spandau, Dermatologie und Allergologie
      • Dresden,, Germany, 01307
        • Recruiting
        • Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie
      • Erfurt, Germany, 99089
        • Recruiting
        • Helios Klinikum Erfurt, Dermatologie und Allergologie
      • Essen, Germany
        • Recruiting
        • Universitatsklinikum Essen Klinik fur Dermatologie Studienambulanz
      • Freiburg, Germany, 79104
        • Recruiting
        • Universitaetsklinikum Freiburg, Klinik fuer Dermatologie und Venerologie
      • Heidelberg, Germany, 69120
        • Recruiting
        • Universitaetsklinikum Heidelberg, NCT-Dermatoonkologie
      • Koeln, Germany, 50937
        • Recruiting
        • Universitaetsklinikum Koeln, Dermatologie und Venerologie,
      • Leipzig, Germany, 04103
        • Recruiting
        • Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
      • Luebeck, Germany, 23538
        • Recruiting
        • Universitaetsklinikum Schleswig Holstein - Campus Luebeck
      • Mainz, Germany, 55131
        • Recruiting
        • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz, Hautklinik
      • Mannheim, Germany, 68167
        • Recruiting
        • Universitaetsklinikum Mannheim, Klinik f. Dermatologie, Venerologie, Allergologle,
      • Tuebingen, Germany, 72076
        • Recruiting
        • Studienzentrum Dermao-Onkologie, Universitaetsklinikum Tuebingen
  • Italy
      • Bari, Italy, 70124
        • Recruiting
        • IRCCS Giovanni Paolo II Oncologia Medica
      • Bologna, Italy, 40138
        • Recruiting
        • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
      • Misterbianco, Italy, 95045
        • Recruiting
        • Humanitas Istituto Clinico Catanese, U.O. Oncologia Medica
      • Napoli, Italy, 80131
        • Recruiting
        • Istituto Nazionale Tumori Fondazione G. Pascale, Oncologia Medica e Terapia Innovativa
      • Palermo, Italy, 90127
        • Recruiting
        • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone - U.O. Oncologia Medica
      • Perugia, Italy, 06132
        • Recruiting
        • A.O.S. Maria della Misericordia, Oncologia Medica
      • Roma, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Siena, Italy, 53100
        • Recruiting
        • A.O.U Senese Policlinico Santa Maria alle Scotte-UOC Immunoterapia Oncologica
      • Verona, Italy, 37134
        • Recruiting
        • Policlinico G.B. Rossi-Borgo Roma-Centro Ricerche Cliniche di Verona
    • Milano
      • Milan, Milano, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Milan, Milano, Italy, 20122
        • Recruiting
        • Fondazione IRCCS CA'Granda Ospedale Maggiore Policlinico-Oncologia Medica
  • Japan
      • Fukuoka, Japan, 811-1395
        • Recruiting
        • National Hospital Organization Kyushu Cancer Center
      • Niigata, Japan, 951-8566
        • Recruiting
        • Niigata Cancer Center Hospital
      • Okayama, Japan, 700-8558
        • Recruiting
        • Okayama University Hospital
      • Osaka, Japan, 541-8567
        • Recruiting
        • Osaka Prefectural Hospital Organization Osaka International Cancer Institute
    • Nagano
      • Matsumoto, Nagano, Japan, 390-8621
        • Recruiting
        • Shinshu University Hospital
    • Osaka
      • Chuo Ku, Osaka, Japan, 540-0006
        • Recruiting
        • National Hospital Organization Osaka National Hospital
    • Sunto-gun
      • Nagaizumi-cho, Sunto-gun, Japan, 411-8777
        • Recruiting
        • Shizuoka Cancer Center
    • Tokho
      • Koto-Ku, Tokho, Japan, 135-8550
        • Recruiting
        • The Cancer Institute Hospital of JFCR
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Severance Hospital Yonsei University Health System
    • Gyeonggi
      • Seoul, Gyeonggi, Korea, Republic of, 03722
        • Recruiting
        • Severance Hospital Younsei University Health System,
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
        • Recruiting
        • National Cancer Center
      • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13496
        • Recruiting
        • CHA University Bundang Medical Center
      • Seoul, Gyeonggi-do, Korea, Republic of, 58128
        • Recruiting
        • Kangbuk Samsung Hospital
    • Jeollanam-do
      • Hwasun, Jeollanam-do, Korea, Republic of, 58128
        • Recruiting
        • Chonnam National University Hwasun Hospital
    • Jung-gu
      • Daejeon, Jung-gu, Korea, Republic of, 35015
        • Recruiting
        • Chungnam National University Hospital
  • New Zealand
      • Auckland, New Zealand
        • Recruiting
        • Auckland City Hospital
      • Hamilton, New Zealand
        • Recruiting
        • Waikato Hospital
      • Tauranga, New Zealand, 3112
        • Recruiting
        • Tauranga Hospital
  • Puerto Rico
      • Rio Piedras, Puerto Rico, 00935
        • Recruiting
        • Hospial Oncologico, Puerto Rico Medical Center
  • Singapore
      • Singapore, Singapore, 169610
        • Recruiting
        • National Cancer Centre
  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2196
        • Recruiting
        • The Medical Oncology Centre of Rosebank
      • Pretoria, Gauteng, South Africa, 0081
        • Recruiting
        • Wilgers Oncology Centre
      • Pretoria, Gauteng, South Africa, 0084
        • Recruiting
        • Curo Oncology
      • Roodepoort, Gauteng, South Africa, 1709
        • Recruiting
        • West Rand Oncology Centre Flora Clinic
    • Western Cape
      • George, Western Cape, South Africa, 6529
        • Recruiting
        • Excellentis Clinical Trial Consultants
      • Kraaifontein, Western Cape, South Africa, 7570
        • Recruiting
        • Cape Town Oncology Trials Cape Gate Oncology Centre
      • Rondebosch, Western Cape, South Africa, 7700
        • Recruiting
        • Cancercare Rondebosch Oncology
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08036
        • Recruiting
        • Hospital Clínic de Barcelona
      • Barcelona, Spain
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08908
        • Recruiting
        • Catalan Institute of Oncology
      • Barcelona, Spain, 08916
        • Recruiting
        • ICO Badalona-Hospital Universitari Germans Trias I Pujol
      • Madrid, Spain, 28050
        • Recruiting
        • Centro Integral Oncológico Clara Campal
      • Madrid, Spain, 28033
        • Recruiting
        • MD Anderson Cancer Center
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Clinico San Carlos
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Regional Universitario de Malaga
      • Sevilla, Spain
        • Recruiting
        • Hospital Universitario Virgen Macarena
      • Zaragoza, Spain
        • Recruiting
        • Hospital Universitario Miguel Servet
  • United Kingdom
      • Edinburgh, United Kingdom, EH4 2XU
        • Recruiting
        • Edinburgh Cancer Center Western General Hospital
    • Hampshire
      • Eastleigh, Hampshire, United Kingdom, SO53 2DW
        • Recruiting
        • Nuffield Health Wessex Hospital
  • United States
    • California
      • Bakersfield, California, United States, 93309
        • Recruiting
        • Comprehensive Blood and Cancer Center
      • La Jolla, California, United States, 92037
        • Recruiting
        • UC San Diego Moores Cancer Center
      • Pasadena, California, United States, 91105
        • Recruiting
        • Innovative Clinical Research Institute (ICRI)
      • Redlands, California, United States, 92373
        • Recruiting
        • Emad Ibrahim, Md, Inc
      • Riverside, California, United States, 92505
        • Recruiting
        • Kaiser Permanente Oncology Research
      • San Marcos, California, United States, 92069
        • Recruiting
        • California Cancer Associates for Research and Excellence, Inc. (cCARE)
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Recruiting
        • Boca Raton Regional Hospital, Lynn Cancer Institute
      • Hollywood, Florida, United States, 33021
        • Recruiting
        • Memorial Regional Hospital
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • Baptist MD Anderson Cancer Center
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Health
      • Pensacola, Florida, United States, 32504
        • Recruiting
        • Ascension Sacred Heart Medical Oncology
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Recruiting
        • Goshen Center for Cancer Care
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
        • Recruiting
        • St. Elizabeth Healthcare
      • Lexington, Kentucky, United States, 40503
        • Recruiting
        • Baptist Health Lexington
    • Maryland
      • Frederick, Maryland, United States, 21701
        • Recruiting
        • Frederick Memorial Healthcare System
    • Missouri
      • Bridgeton, Missouri, United States, 63044
        • Recruiting
        • St Louis Cancer Care
      • Kansas City, Missouri, United States, 64114
        • Recruiting
        • AMR Kansas City
      • Saint Joseph, Missouri, United States, 64506
        • Recruiting
        • MediSearch Clinical Trials
    • Montana
      • Billings, Montana, United States, 59102
        • Recruiting
        • St. Vincent - Frontier Cancer Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Levine Cancer Institute
      • Goldsboro, North Carolina, United States, 27534
        • Recruiting
        • Southeastern Medical Oncology Center
    • Ohio
      • Canton, Ohio, United States, 44718
        • Recruiting
        • Gabrail Cancer Center Research
      • Toledo, Ohio, United States, 43623
        • Recruiting
        • Toledo Clinic Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Medical Oncology Clinic
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • Recruiting
        • AnMed Health
      • Lancaster, South Carolina, United States, 29720
        • Recruiting
        • Carolina Blood and Cancer Care Associates
    • Texas
      • The Woodlands, Texas, United States, 77380
        • Recruiting
        • Renovatio Clinical
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Recruiting
        • Utah Cancer Specialists
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert Hospital, Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histopathologically confirmed diagnosis of non-uveal, Stage III (unresectable), or Stage IV (metastatic) melanoma according to AJCC staging system (8th edition).
  2. Known BRAF V600 mutation status or consent to BRAF V600 mutation testing before randomization.

  3. Tumor tissue available for PD-L1 testing at central lab. 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 from an unresectable or metastatic site is available prior to the start of the Screening Phase, patients must consent to allow the acquisition of additional tumor tissue for assessment of the biomarker.

  4. Males or females 12 years of age or older.
  5. ECOG performance status ≤1 for age ≥18 years, Lansky performance score ≥80% for age 12 to 17 years.

  6. At least one measurable lesion defined by RECIST 1.1 criteria, (separate from the lesion to be used for tumor tissue collection for PD-L1 testing) 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).

  7. 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-CTLA-4) is allowed if disease progression/or recurrence occurred at least 6 months after the last dose 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
  8. 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

  9. 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).
  10. Negative serum pregnancy test at baseline for women of childbearing potential.
  11. 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.
  12. Have the ability to understand and the willingness to sign a written informed consent document, comply with study scheduled treatment, visits and assessments.

Exclusion Criteria:

  1. History of ≥ Grade 3 hypersensitivity reactions to monoclonal antibodies.
  2. 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.
  3. 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; 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.
  4. Uncontrolled hypertension, systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >100 mmHg.
  5. Patients with new, active, or progressive brain metastases or leptomeningeal disease with except when considered for a separate special open-label cohort described in protocol Section 5.3 or "Inclusion of Patients with Progressive Brain Metastasis" section in the protocol synopsis.
  6. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer, or bowel resection that affects absorption of orally administered drugs.
  7. 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.
  8. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
  9. Known history of testing positive for HIV, known AIDS.
  10. Hepatitis B surface antigen positive or hepatitis C antibody positive. Further investigation per institutional practices may be performed to exclude active infection.
  11. 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.
  12. Use of another investigational agent (drug or vaccine not marketed for any indication) 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
  13. Pregnant or breast-feeding women.

  14. Second 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
    • Carcinoma in situ of the cervix treated with curative intent
    • Prostate cancer treated with curative intent with serum prostate specific antigen (PSA) < 2.0 ng/mL
  15. Patients with medical conditions requiring administration of strong cytochrome P450 (CYP), CYP3A4 Inducers and Inhibitors.
  16. Uncontrolled adrenal insufficiency or active chronic liver disease.
  17. 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.
  18. 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.
  19. Unwilling or unable to comply with procedures required in this protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Test Arm
HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days
Drug: HBI-8000 in combination with nivolumab
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.
Other Names:
  • For HBI-8000: tudicdinostat; For nivolumab: OPDIVO®
Placebo Comparator: Control Arm
Placebo oral BIW + nivolumab IV at specific doses on specific days
Drug: Placebo in combination with nivolumab
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.
Other Names:
  • For nivolumab: OPDIVO®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Outcome
Time Frame: From date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months
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).
From date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months
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 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Outcome
Time Frame: From date of randomization to death due to any cause, assessed up to 48 months
Overall Survival (OS) defined as the time from date of randomization to the date of death due to any cause.
From date of randomization to death due to any cause, assessed up to 48 months
Secondary Outcome
Time Frame: From date of randomization until the end of study, assessed up to 48 months
Safety defined as incidence rate of adverse events (AEs), severity (CTCAE v.5.0), causal relationship assessment, and outcomes of reported AEs.
From date of randomization until the end of study, assessed up to 48 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Other Outcome Measures
Time Frame: Assessed up to 48 months
Duration of Response (DoR) defined as the time from the first date of PR or better as determined by BIRC to the first date of PD or death from any cause.
Assessed up to 48 months
Other Outcome Measures
Time Frame: Assessed up to 48 months
Disease Control Rate (DCR) defined as the percentage of patients enrolled in each study arm with best overall response of CR, PR or stable disease (SD) as determined by BIRC.
Assessed up to 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

HUYABIO International, LLC.

Collaborators

Bristol-Myers Squibb

Investigators

  • Study Director: John T Ning, MD, PhD, HUYABIO International, LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 12, 2021

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

October 1, 2025

Study Registration Dates

First Submitted

December 7, 2020

First Submitted That Met QC Criteria

December 14, 2020

First Posted (Actual)

December 19, 2020

Study Record Updates

Last Update Posted (Actual)

July 27, 2023

Last Update Submitted That Met QC Criteria

July 25, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HBI-8000-303

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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