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

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Unresectable or Metastatic Melanoma, Progressive Brain Metastasis

In brief

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.

Key facts

Study ID

NCT04674683

Run by

HUYABIO International, LLC.

People needed

450

Starts

2021-08-12

Expected to finish

2026-12-01

Last updated by the study team

2025-09-24

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

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.
• 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.

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:
• 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.

Where it is running

• UC San Diego Moores Cancer Center — La Jolla, California, United States
• Innovative Clinical Research Institute (ICRI) — Pasadena, California, United States
• Emad Ibrahim, MD, INC — Redlands, California, United States
• Kaiser Permanente Oncology Research — Riverside, California, United States
• California Cancer Associates for Research and Excellence, Inc. (cCARE) — San Marcos, California, United States
• Boca Raton Regional Hospital, Lynn Cancer Institute — Boca Raton, Florida, United States
• Memorial Regional Hospital — Hollywood, Florida, United States
• Baptist MD Anderson Cancer Center — Jacksonville, Florida, United States
• Orlando Health — Orlando, Florida, United States
• Ascension Sacred Heart Medical Oncology — Pensacola, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Goshen Center for Cancer Care — Goshen, Indiana, United States
• St. Elizabeth Healthcare — Edgewood, Kentucky, United States
• Baptist Health Lexington — Lexington, Kentucky, United States
• Frederick Memorial Healthcare System — Frederick, Maryland, United States
• St Louis Cancer Care — Bridgeton, Missouri, United States
• AMR Kansas City — Kansas City, Missouri, United States
• Medisearch Clinical Trials — Saint Joseph, Missouri, United States
• St. Vincent - Frontier Cancer Center — Billings, Montana, United States
• Levine Cancer Institute — Charlotte, North Carolina, United States
• Southeastern Medical Oncology Center — Goldsboro, North Carolina, United States
• Gabrail Cancer Center Research — Canton, Ohio, United States
• Toledo Clinic Cancer Center — Toledo, Ohio, United States
• Thomas Jefferson University Medical Oncology Clinic — Philadelphia, Pennsylvania, United States
• Comprehensive Blood and Cancer Center — Bakersfield, California, United States

Full record on ClinicalTrials.gov

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