Health Condition 1: C439- Malignant melanoma of skin, unspecified
Conditions
Interventions
Intervention1: HBI-8000 (tucidinostat) versus Placebo: Parallel Assignment
This is a double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab.
Patients will take 3
Sponsors
HUYABIO International, LLC
Eligibility
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 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 • PD-L1 negative 4. Males or females 18 years of age or older. 5. ECOG performance status less than equal 1. 6. At least one measurable lesion defined by RECIST v1.1 criteria, (separate from the lesion to be used for tumor tissue collection for PD-L1 testing) not counting brain metastasis with • Longest diameter more than equal 10 mm by computed tomography (CT) (when slice thickness is less than equal 5 mm); or more than equal to 2 times of slice thickness (when slice thickness is more than 5 mm) • Pathologically enlarged lymph node: more than equal to 15 mm in short axis by CT (when slice thickness is less than equal to 5 mm) • Clinical: More than 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 a. BRAF mutation targeting therapy more than 4 weeks before administration of Study Treatment. b. 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 c. Adjuvant interferon therapy must have been completed more than 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 10. Negative serum pregnancy test at baseline for women of childbearing potential (WOCBP). 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 an adequate method of contraception including a highly effective method and a barrier method from study start, during the study, and for 5 months after the last dose of Study Drug. Highly effective contraception used by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 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
Exclusion criteria: Patients who fulfill any of the following criteria at Screening will not be eligible for admission into the study: 1. History of more than equal 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. Recipient of solid organ transplant 4. History of a cardiovascular illness including: congestive heart failure (New York Heart Association Grade III or IV) 5. Uncontrolled hypertension, systolic blood pressure (SBP) more than 160 mmHg or diastolic blood pressure (DBP) more than 100 mmHg. 6. Patients with new, active, or progressive brain metastases or leptomeningeal disease except when considered for a separate special open-label cohort 7. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer, or bowel resection that affects absorption of orally administered drugs. 8. 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. 9. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy. 10. Known history of testing positive for HIV, known AIDS. 11. Hepatitis B surface antigen positive or hepatitis C antibody positive. 12. Patients with a condition requiring chronic systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days before administration of Study Treatment. Inhaled or topical steroids, or adrenal replacement dose of corticosteroids at dose less than equal to 10 mg/day prednisone equivalent are permitted. 13. 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 use within 3 months before administration of Study Treatment. 14. Pregnant or breast-feeding women. 15. 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) less than 2.0 ng/mL 16. Patients with medical conditions requiring administration of strong cytochrome P450 (CYP)3A4 inducers and inhibitors. 17. Uncontrolled adrenal insufficiency or active chronic liver disease. 18. 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 components are allowed. However, intranasal influenza vaccines (e.g., Flu-Mist) are not allowed. Coronavirus disease 2019 (COVID-19) vaccination should be administered at least 7 days before Cycle 1 Day 1. 19. Underlying medical conditions that, in the Investigatorâ??s opinion, will make the ad
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. 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. 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: ORR will be evaluated from date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months. PFS will be evaluated from date of randomization to the earliest date of documented progressive disease (PD), assessed up to 48 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) defined as the time from date of randomization to the date of death due to any cause.Timepoint: From date of randomization to death due to any cause, 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.Timepoint: From date of randomization until the end of study, assessed up to 48 months | — |
Countries
Australia, Austria, Belgium, Brazil, Czech Republic, France, Germany, India, Italy, New Zealand, Republic of Korea, Singapore, South Africa, Spain, United Kingdom, United States of America
Contacts
Public ContactKanhaiya Choudhary
Novotech India Private Limited
Outcome results
None listed