Melanoma Clinical Trial

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

Summary

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.

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Full 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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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. 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.

Males or females 12 years of age or older.
ECOG performance status ≤1 for age ≥18 years, Lansky performance score ≥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 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).

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
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 serum albumin ≥ 3.0 gdL).
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.

Exclusion Criteria:

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.
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.
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 described in protocol Section 5.3 or "Inclusion of Patients with Progressive Brain Metastasis" section in the protocol synopsis.
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) 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.

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
Patients with medical conditions requiring administration of strong cytochrome P450 (CYP), CYP3A4 Inducers and Inhibitors.
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.
Unwilling or unable to comply with procedures required in this protocol.

Study is for people with:

Melanoma

Phase:

Phase 3

Estimated Enrollment:

480

Study ID:

NCT04674683

Recruitment Status:

Recruiting

Sponsor:

HUYABIO International, LLC.

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There are 86 Locations for this study

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Innovative Clinical Research Institute (ICRI)
Pasadena California, 91105, United States
Emad Ibrahim, MD, INC
Redlands California, 92373, United States
Kaiser Permanente Oncology Research
Riverside California, 92505, United States
California Cancer Associates for Research and Excellence, Inc. (cCARE)
San Marcos California, 92069, United States
Boca Raton Regional Hospital, Lynn Cancer Institute
Boca Raton Florida, 33486, United States
Memorial Regional Hospital
Hollywood Florida, 33021, United States
Baptist MD Anderson Cancer Center
Jacksonville Florida, 32207, United States
Orlando Health
Orlando Florida, 32806, United States
Ascension Sacred Heart Medical Oncology
Pensacola Florida, 32504, United States
Moffitt Cancer Center
Tampa Florida, 33612, United States
Goshen Center for Cancer Care
Goshen Indiana, 46526, United States
Baptist Health Lexington
Lexington Kentucky, 40503, United States
Frederick Memorial Healthcare System
Frederick Maryland, 21701, United States
St Louis Cancer Care
Bridgeton Missouri, 63044, United States
AMR Kansas City
Kansas City Missouri, 64114, United States
Medisearch Clinical Trials
Saint Joseph Missouri, 64506, United States
St. Vincent - Frontier Cancer Center
Billings Montana, 59102, United States
Levine Cancer Institute
Charlotte North Carolina, 28204, United States
Southeastern Medical Oncology Center
Goldsboro North Carolina, 27534, United States
Gabrail Cancer Center Research
Canton Ohio, 44718, United States
Thomas Jefferson University Medical Oncology Clinic
Philadelphia Pennsylvania, 19107, United States
Renovatio Clinical
The Woodlands Texas, 77380, United States
Utah Cancer Specialists
Salt Lake City Utah, 84106, United States
Inova Schar Cancer Institute
Fairfax Virginia, 22031, United States
Froedtert Hospital, Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States
Sydney Adventist Hospital
Wahroonga New South Wales, , Australia More Info
Nina Singh
Contact
[email protected]
University of the Sunshine Coast
Buderim Queensland, 4556, Australia More Info
Susan Poechhacker
Contact
61 7 5456 5515
[email protected]
Hong Shue, M.D.
Principal Investigator
University of the Sunshine
Sippy Downs Queensland, 4556, Australia
Icon Cancer Centre Wesley
South Brisbane Queensland, , Australia More Info
Agnieszka Malczewski, M.D.
Contact
0408206624
[email protected]
Agnieszka Malczewski, M.D.
Principal Investigator
Ballarat Health Services
Ballarat Victoria, , Australia More Info
Virginia Murphy
Contact
+61 3 5320 6732
[email protected]
Donna McIntyre
Contact
+61 3 5320 8624
[email protected]
Sharad Sharma, MD
Principal Investigator
Goulburn Valley Health
Shepparton Victoria, , Australia More Info
Carole Mott
Contact
+61 3 5832 3778
[email protected]
Myron Klevansky, MD
Principal Investigator
Royal Brisband and Women's Hospital
Brisbane , , Australia More Info
Medical Oncology Clinical Trials Unit
Contact
07 3646 7712
[email protected]
Liverpool Hospital
Liverpool , , Australia More Info
Bavanthi Balkrishnar
Contact
02 8738 9744
Affinity Clinical Research
Nedlands , , Australia More Info
Tweed Hospital
Tweed Heads , , Australia
Calvary Mater Newcastle
Waratah , , Australia More Info
C Gedye, MD
Contact
[email protected]
Medical University of Graz Department of Dermatology and Venerology
Graz , 8036, Austria
Univ.-Lkinik für Dermatologie, Venerologie und Allergologie
Innsbruck , 6020, Austria
AZ Klina
Brasschaat , 2930, Belgium
Cliniques Universitaires
Brussels , 1200, Belgium
AZ Maria Middelares
Ghent , 9000, Belgium
Jessa Ziekenhuis
Hasselt , 3500, Belgium
Jessa Ziekenhuis
Hasselt , , Belgium
Hospital de la Citadelle
Liège , 4000, Belgium
Clinique Saint-Pierre
Ottignies , 1340, Belgium
Ensino e Terapia de Inovação Clίnica AMO-ETICA
Salvador Bahia, 41950, Brazil
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer,
Curitiba Paraná, 81520, Brazil
Hospital do Câncer de Londrina
Londrina Paraná, 86015, Brazil
Hospital São Vicente de Paulo
Centro Rio Grande Do Sul, 99010, Brazil
Hospital Bruno Born
Lajeado Rio Grande Do Sul, 95900, Brazil
Centro Gaúcho Integrado de Oncologia, Hematologia
Porto Alegre Rio Grande Do Sul, 90850, Brazil
Hospital de Clίnίcas de Porto Alegre
Santa Cruz Do Sul Rio Grande Do Sul, 96810, Brazil
Oncosite-Centro de Pesquisa Clίnica em Oncologia
São Cristóvão Rio Grande Do Sul, 98700, Brazil
Hopital de Câncer de Barretos-Fundação Pio XII
Barretos Sao Paulo, 14784, Brazil
Fundação Doutor Amaral Carvalho
Jaú São Paulo, 17210, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
São José Do Rio Preto São Paulo, 15090, Brazil
Fakultni nemocnice Olomoue
Olomouc , 77900, Czechia
Fakultni nemocnice Ostrava Kozni oddeleni
Ostrava-Poruba , 70852, Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague , 10034, Czechia
CHU de Besançon - Hôpital Jean MINJOZ
Besançon , , France
Hôpital Ambroise Paré
Boulogne-Billancourt , , France
CHU de Dijon, Service de dermatologie
Dijon , , France
CHU Grenoble Alpes
La Tronche , , France
CHRU Lille - Hôpital Claude Huriez, Clinique de Dermatologie
Lille , , France
Hôpital La Timone
Marseille , 13385, France
Hôpital Saint-Louis
Paris , , France
Centre Hospitalier Lyon Sud
Pierre-Bénite , , France
CHU de Rouen-Hôpital
Rouen , 76031, France
Institut Gustave Roussy, Service de Dermatologie
Villejuif , , France
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
Berlin , 10117, Germany
Vivantes Klinikum Spandau, Dermatologie und Allergologie
Berlin , 13585, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie
Dresden, , 01307, Germany
Helios Klinikum Erfurt, Dermatologie und Allergologie
Erfurt , 99089, Germany
Universitatsklinikum Essen Klinik fur Dermatologie Studienambulanz
Essen , , Germany
Universitaetsklinikum Freiburg, Klinik fuer Dermatologie und Venerologie
Freiburg , 79104, Germany
Universitaetsklinikum Heidelberg, NCT-Dermatoonkologie
Heidelberg , 69120, Germany
Universitaetsklinikum Koeln, Dermatologie und Venerologie,
Koeln , 50937, Germany
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Leipzig , 04103, Germany
Universitaetsklinikum Schleswig Holstein - Campus Luebeck
Luebeck , 23538, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz, Hautklinik
Mainz , 55131, Germany
Universitaetsklinikum Mannheim, Klinik f. Dermatologie, Venerologie, Allergologle,
Mannheim , 68167, Germany
Studienzentrum Dermao-Onkologie, Universitaetsklinikum Tuebingen
Tuebingen , 72076, Germany
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
Bologna , 40138, Italy
Humanitas Istituto Clinico Catanese, U.O. Oncologia Medica
Misterbianco , 95045, Italy
Istituto Nazionale Tumori Fondazione G. Pascale, Oncologia Medica e Terapia Innovativa
Napoli , 80131, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone - U.O. Oncologia Medica
Palermo , 90127, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma , 00168, Italy
A.O.U Senese Policlinico Santa Maria alle Scotte-UOC Immunoterapia Oncologica
Siena , 53100, Italy
Policlinico G.B. Rossi-Borgo Roma-Centro Ricerche Cliniche di Verona
Verona , 37134, Italy
Auckland City Hospital
Auckland , , New Zealand
Waikato Hospital
Hamilton , , New Zealand
Tauranga Hospital
Tauranga , 3112, New Zealand
The Medical Oncology Centre of Rosebank
Johannesburg Gauteng, 2196, South Africa
Wilgers Oncology Centre
Pretoria Gauteng, 0081, South Africa
Curo Oncology
Pretoria Gauteng, 0084, South Africa
West Rand Oncology Centre Flora Clinic
Roodepoort Gauteng, 1709, South Africa
Excellentis Clinical Trial Consultants
George Western Cape, 6529, South Africa
Cape Town Oncology Trials Cape Gate Oncology Centre
Kraaifontein Western Cape, 7570, South Africa
Cancercare Rondebosch Oncology
Rondebosch Western Cape, 7700, South Africa
Hospital Universitari Vall d'Hebron
Barcelona , 08035, Spain
Hospital Clinic de Barcelona
Barcelona , 08036, Spain
Catalan Institute of Oncology
Barcelona , 08908, Spain
ICO Badalona-Hospital Universitari Germans Trias I Pujol
Barcelona , 08916, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona , , Spain
MD Anderson Cancer Center
Madrid , 28033, Spain
Hospital Universitario Fundación Jimenez Diaz
Madrid , 28040, Spain
Centro Integral Oncologico Clara Campal
Madrid , 28050, Spain
Hospital Universitario Clinico San Carlos
Madrid , , Spain
Hospital Regional Universitario de Málaga
Málaga , 29010, Spain
Hospital Universitario Virgen Macarena
Sevilla , , Spain
Hospital Universitario Miguel Servet
Zaragoza , , Spain
Edinburgh Cancer Center Western General Hospital
Edinburgh , EH4 2, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Melanoma

Phase:

Phase 3

Estimated Enrollment:

480

Study ID:

NCT04674683

Recruitment Status:

Recruiting

Sponsor:


HUYABIO International, LLC.

How clear is this clinincal trial information?

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