Metastatic or unresectable melanoma MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Tucidinostat
Product Code: HBI-8000
Pharmaceutical Form: Tablet
INN or Proposed INN: Tucidinostat
CAS Number: 1616493-44-7
Current Sponsor code: HBI-8000
Other descriptive name: Tucidino
Sponsors
HUYABIO International, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients may be entered in the study only if they meet all of the following 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 (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) (see Appendix 5) 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 recovered from all treatment related toxicities: a. BRAF mutation targeted therapy >4 weeks before administration of Study Treatment. b. Adjuvant or neoadjuvant therapy with PD-1 or PD-L1 inhibitors, anti- cytotoxic T lymphocyte-associated protein 4 (CTLA4) 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. c. 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: a. Hematology: white blood cells (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 Hgb =10 g/dl is acceptable. b. Creatinine clearance (CrCL) =30 mL/min using Cockcroft-Gault formula. c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 × ULN, alkaline phosphatase =2.5 × ULN unless bone metastases present (patients with documented bone metastases: alkaline phosphatase <5 × 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 t
Exclusion criteria
Exclusion criteria: Exclusion Criteria Patients who fulfill any of the following criteria at Screening will not be eligible for admission into the study: 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 Fridericia’s correction formula (QTcF) >450 ms in male or >470 ms in female, 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, except when considered for a separate open label cohort for special population. 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 human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (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 (or equivalent) are permitted. 12. Use of other investigational agent (drug or vaccine not marketed for any indication) within 28 days 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. Received approved live vaccine/ live attenuated vaccines within 30 days of planned Cycle 1 Day 1. Inactivated viral vaccines or vaccines based on subviral component are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are not allowed. C
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Co-primary Objectives: To compare, between Test (HBI-8000 + nivolumab) and Control (placebo + nivolumab) arms: • Objective Response Rate (ORR), defined as the percentage of patients enrolled in each study arm with a best response of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the blinded independent review committee (BIRC) • Progression-free Survival (PFS), defined as the time from the date of randomization to the first date of documented progression as determined by BIRC, or the date of death due to any cause, whichever occurs first.;Secondary Objective: To compare, between Test and Control arms: • Overall Survival (OS) defined as the time from the date of randomization to the date of death due to any cause. • Safety defined as incidence rate of adverse events, severity (CTCAE), causal relationship assessment, and outcomes at the time of randomization until the end of study.;Primary end point(s): 1.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). 2.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. ;Timepoint(s) of evaluation of this end point: 48 Months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Overall Survival (OS) defined as the time from the date of randomization to the date of death due to any cause. 2. Safety defined as incidence rate of adverse events, severity (CTCAE), causal relationship assessment, and outcomes at the time of randomization until the end of study ;Timepoint(s) of evaluation of this end point: 48 Months | — |
Countries
Australia, Austria, Belgium, Brazil, Czechia, Czech Republic, France, Germany, Italy, New Zealand, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactSenior Director, Clinical Operation
HUYABIO International, LLC
Outcome results
None listed