What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly those involving immune checkpoint inhibitors like Nivolumab (a PD-1 inhibitor) and combination therapies with Ipilimumab (a CTLA-4 inhibitor), are associated with a range of immune-related adverse events. These can include skin reactions, endocrine issues, gastrointestinal problems, and autoimmune conditions affecting various organs. Severe side effects may involve pneumonitis, colitis, hepatitis, and endocrinopathies. Combination therapies tend to have higher rates of these adverse events compared to monotherapy.

What prior FDA approvals exist?

The FDA has approved several treatments for melanoma, particularly focusing on immune checkpoint inhibitors such as nivolumab and pembrolizumab. These drugs are often used alone or in combination with other agents like ipilimumab to treat advanced or metastatic melanoma. While the context does not provide specific details on the approval of HDAC inhibitors combined with PD-1 inhibitors, it highlights the efficacy of combination therapies in improving treatment outcomes for melanoma patients.

What other types of research exist?

Promising alternatives to HBI-8000 combined with Nivolumab for melanoma patients include: 1) Pembrolizumab combined with Vorinostat, as explored in the PEVO basket trial for squamous cell carcinomas, which may be applicable to melanoma. 2) Talimogene laherparepvec (T-VEC) combined with Pembrolizumab, as studied in the MASTERKEY-265 phase 1b trial for advanced melanoma. 3) Dual checkpoint inhibition with Nivolumab and Ipilimumab, particularly for patients with MSI-H tumors or those who have acquired resistance to prior anti-PD-1 therapy.

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Epigenetic Modulator

HBI-8000 + Nivolumab for Melanoma

Phase 3

Waitlist Available

Led By Agnieszka Malczewski, MD,PhD,FAIC

Research Sponsored by HUYA Bioscience International

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have not received anti-PD-1, anti-PD-L1 or other systemic therapy for unresectable or metastatic melanoma

Known BRAF V600 mutation status or consent to BRAF V600 mutation testing before randomization

Must not have

History of ≥ Grade 3 hypersensitivity reactions to monoclonal antibodies

History of a cardiovascular illness

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed up to 48 months

Awards & highlights

Pivotal Trial

Summary

This trial tests a pill called HBI-8000 with an IV drug called nivolumab in patients with advanced melanoma. It targets patients whose cancer cannot be surgically removed or has spread, including to the brain. The treatment works by enhancing the immune system's ability to fight cancer.

Who is the study for?

This trial is for adults and children (12+) with advanced melanoma that hasn't spread to the brain. Participants must not have had prior treatments targeting PD-1/PD-L1 pathways, be willing to use birth control, and able to follow the study plan. They should not have HIV/AIDS, hepatitis B/C, other cancers unless in remission for 2 years, or conditions requiring strong immune system drugs.

What is being tested?

The study compares HBI-8000 combined with nivolumab against a placebo with nivolumab in patients with unresectable or metastatic melanoma. It's designed to see which treatment is more effective and safe. Patients are grouped based on their PD-L1 expression levels and LDH enzyme amounts.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation of organs, fatigue, skin issues like rash or itching, digestive problems like nausea or diarrhea, potential liver function changes and an increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I haven't had specific immune therapies for advanced melanoma.

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I know my BRAF V600 mutation status or agree to testing.

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My melanoma is confirmed at an advanced stage and cannot be surgically removed.

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I am 18 or older and can care for myself; or I am 12-17 and mostly active.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had severe allergic reactions to monoclonal antibody treatments.

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I have a history of heart disease.

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I am currently fighting a serious infection that needs treatment.

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I have tested positive for HIV/AIDS.

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I have been in remission from another cancer for 2 years or it is easily treatable.

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I am on long-term steroids or other drugs that affect my immune system.

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I have not received a live vaccine within the last 30 days.

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I have an autoimmune disease.

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I have been treated with immune-targeting drugs for advanced melanoma.

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I have a history of severe diarrhea, bowel disease, stomach ulcers, or surgery that affects drug absorption.

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I have new or worsening brain metastases or leptomeningeal disease.

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I do not have uncontrolled adrenal issues or ongoing liver disease.

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My high blood pressure is not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ assessed up to 48 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~assessed up to 48 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and assessed up to 48 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Secondary study objectives

Objective Response Rate

Overall Survival

Safety, defined as the incidence rate of AEs

Other study objectives

Disease Control Rate

Duration of Response

Time to Progression

+1 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Test ArmExperimental Treatment1 Intervention

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

Group II: Control ArmPlacebo Group1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

HBI-8000 in combination with nivolumab

2016

Completed Phase 2

~100

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Melanoma treatments often involve immunotherapy, which leverages the body's immune system to target and destroy cancer cells. Nivolumab, a PD-1 inhibitor, works by blocking the programmed cell death-1 (PD-1) pathway, thereby preventing cancer cells from evading immune detection. HBI-8000, an HDAC inhibitor, modifies the expression of genes involved in cancer cell survival and immune response, potentially enhancing the effectiveness of immunotherapy. For melanoma patients, these mechanisms are crucial as they offer a targeted approach to treatment, improving the immune system's ability to fight cancer and potentially leading to better outcomes.