Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Melanoma

Neoplasm Metastasis

Brain Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days

Placebo oral BIW + nivolumab IV at specific doses on specific days

Patients will take 30 mg of HBI-8000 orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV will be administered by intravenous infusion at specific doses on specific days in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice. In adolescent patients with body weight \< 40 kg, nivolumab will be dosed at specific doses on specific days.

HBI-8000 in combination with nivolumab

Patients will take 30 mg of Placebo orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV at specific doses will be administered by intravenous infusion in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice.

Placebo in combination with nivolumab

M Tawashi

Nina Singh

Susan Poechhacker

Hong Shue, M.D.

Agnieszka Malczewski, M.D.

Virginia Murphy

Donna McIntyre

Sharad Sharma, MD

Carole Mott

Myron Klevansky, MD

Medical Oncology Clinical Trials Unit

Bavanthi Balkrishnar

Nursing

C Gedye, MD

John T Ning, MD, PhD

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.

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.

This is a double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab.

All Eligible patients will be randomized within the appropriate stratum at a 1:1 ratio to the Test arm or the Control arm, with the exception of Cohort for special population.

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

A Multicenter, Randomized, Double-Blind Phase 3 Study of HBI-8000 Combined With Nivolumab Versus Placebo With Nivolumab in Patients With Unresectable or Metastatic Melanoma Not Previously Treated With PD-1 or PD-L1 Inhibitors

Duration of Response (DoR) defined as the time from the first date of PR or better as determined by BIRC to the first date of PD or death from any cause.

Disease Control Rate (DCR) defined as the percentage of patients enrolled in each study arm with best overall response of CR, PR or stable disease (SD) as determined by BIRC.

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).

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.

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.

Spots Global Cancer Trial Database for progressive brain metastasis