A Randomized, Double-Blind, Phase III Study Comparing Investigational Drug HBI-8000 Combined With Nivolumab vs. Placebo with Nivolumab in Patients With Advanced Melanoma

JRCT ID: jRCT2061220112

Registered date:27/03/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Unresectable or Metastatic Melanoma
• Date of first enrollment: 09/05/2023
• Target sample size: 30
• Countries of recruitment: USA,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Czech Republic,Japan,France,Japan,Germany,Japan,Italy,Japan,New Zealand,Japan,Puerto Rico,Japan,South Africa,Japan,Spain,Japan,UK,Japan,Singapore,Japan,South Korea,Japan
• Study type: Interventional

Intervention(s)

Development code, Generic name of investigational material etc.: HBI-8000, Tucidinostat (Hiyasta(R) Tablets)
Generic name of control material etc.: Placebo
Generic name of concomitant material etc.: nivolumab (OPDIVO(R))

A treatment cycle consists of 28 days. After randomization, 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
Study treatment continue up to 2 years or until disease progression, unacceptable toxicity, new cancer treatment or patient withdrawal of consent occurs.

Outcome(s)

• Primary Outcome: - Progression-free Survival (PFS) defined as the time (in days) 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.

Secondary Outcome

- Objective Response Rate (ORR) defined as the percentage of patients enrolled in each study arm with a best response of confirmed CR or PR as determined by BIRC.
- Overall Survival (OS) defined as the time from date of randomization to the date of death due to any cause.
- Safety defined as incidence rate of adverse events (AEs), severity (CTCAE v.5.0), causal relationship assessment, and outcomes of reported AEs.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Histopathologically confirmed diagnosis of non-uveal, Stage III (unresectable), or Stage IV (metastatic) melanoma according to AJCC staging system (8th edition).
-Males or females 18 years of age or older.
-Eastern Cooperative Oncology Group (ECOG) performance status <=1.
-At least one measurable lesion defined by RECIST 1.1 criteria separate from the lesion to be used for tumor tissue collection
-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 targeted 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 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

Exclude criteria

-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.
-Patients with new, active, or progressive brain metastases or leptomeningeal disease.
-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.
-Pregnant or breast-feeding women.
-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.
-Patients with a history of or active interstitial lung disease (ILD) or non-infectious pneumonitis.

Related Information

• Primary Sponsor: Onogi Hiroshi
• Source(s) of Monetary Support: Meiji Seika Pharma Co., Ltd.
• Secondary ID(s): NCT04674683,2019-002521-30