HBI-8000 + Nivolumab for Melanoma

Not currently recruiting at 155 trial locations

Overseen By M Tawashi

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: HUYA Bioscience International

Must not be taking: Corticosteroids, Immunosuppressants, CYP3A4 drugs, others

Disqualifiers: Cardiovascular illness, Autoimmune disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: Up to 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with serious skin cancer, specifically unresectable or metastatic melanoma. The researchers compare the safety and effectiveness of two drugs, HBI-8000 (a potential new drug) and nivolumab (also known as Opdivo, an immunotherapy drug), against a placebo with nivolumab. It also includes a special group for those with new or worsening brain metastasis. Individuals with melanoma that cannot be surgically removed or has spread, and who have not received certain prior treatments, may qualify to participate. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it excludes patients who need certain medications like strong cytochrome P450 inducers and inhibitors, or those requiring chronic systemic corticosteroids above a certain dose. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

An earlier study found the combination of HBI-8000 and nivolumab to be safe for patients with advanced melanoma. Almost two-thirds of these patients responded well to the treatment. Some side effects, such as tiredness, diarrhea, and skin problems, were noted but are generally manageable. The combination has shown promising results, and the current phase of the study aims to further confirm its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Researchers are excited about the combination of HBI-8000 and Nivolumab for melanoma because HBI-8000 offers a unique mechanism of action. Unlike traditional treatments that primarily target specific cancer cell pathways, HBI-8000 is a histone deacetylase inhibitor that modifies gene expression, potentially enhancing the immune system's ability to fight cancer. This drug is combined with Nivolumab, an immune checkpoint inhibitor, which helps unleash the immune system against cancer cells by blocking a pathway that restricts immune response. Together, these treatments may provide a more comprehensive approach to tackling melanoma, offering hope for improved outcomes.

What evidence suggests that HBI-8000 combined with nivolumab could be an effective treatment for melanoma?

Previous studies have shown promising results for the combination of HBI-8000 and nivolumab in patients with advanced melanoma. Nearly two-thirds of patients responded well to this treatment when they had not received prior anti–PD-1/PD-L1 therapy. In this trial, participants in the test arm will receive HBI-8000, a pill that complements nivolumab, an approved cancer drug, to help the body's immune system attack cancer cells. Nivolumab alone has already caused long-lasting tumor shrinkage in advanced melanoma cases. These findings suggest that using HBI-8000 with nivolumab could effectively treat advanced melanoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Gloria Lee, MD, PhD

Principal Investigator

HUYABIO International, LLC.

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Women who could become pregnant must have a negative pregnancy test before starting the study.

You have tumor tissue that can be tested for PD-L1 at a central laboratory.

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

I have had severe allergic reactions to monoclonal antibody treatments.

I have a history of heart disease.

Pregnant or breast-feeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HBI-8000 or Placebo combined with nivolumab in 28-day cycles, continuing up to 2 years or until disease progression, unacceptable toxicity, or withdrawal of consent

Up to 104 weeks

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

Open-label extension (optional)

A separate cohort of adults with new, progressive brain metastasis or adolescents with or without new progressive brain metastasis receive HBI-8000 combined with nivolumab

As per cohort schedule

What Are the Treatments Tested in This Trial?

Interventions

• HBI-8000
• Nivolumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Test Arm Experimental Treatment 1 Intervention

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

Group II: Control Arm Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

HUYA Bioscience International

Lead Sponsor

Trials

9

Recruited

870+

HUYABIO International, LLC.

Lead Sponsor

Trials

12

Recruited

960+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Nivolumab (Opdivo) monotherapy led to complete regression of local recurrence and multiple lung metastases in a patient with recurrent skin melanoma and a positive BRAF mutation, demonstrating its efficacy as a treatment option.

After 5 courses of nivolumab, the patient experienced significant improvement in her condition, achieving an ECOG performance status of 0, indicating a return to an active lifestyle without pain, and normal serum LDH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. Samsonia, M., Kandelaki, M., Gibradze, O., et al.[2021]

In a phase 3 trial involving 405 patients with advanced melanoma, nivolumab resulted in a significantly higher objective response rate (31.7%) compared to investigator's choice of chemotherapy (10.6%), indicating its superior efficacy as a treatment option.

Nivolumab was associated with fewer severe adverse effects compared to chemotherapy, with only 5% of patients experiencing serious drug-related side effects, suggesting it is a safer alternative for patients who have progressed after previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Weber, JS., D'Angelo, SP., Minor, D., et al.[2022]

Nivolumab is shown to be the most cost-effective treatment option for advanced melanoma patients in England, with incremental cost-effectiveness ratios of £24,483 for BRAF mutation-negative and £17,362 for mutation-positive patients.

The analysis utilized a Markov state-transition model based on patient-level data from clinical trials, indicating that nivolumab provides long-term survival benefits while being economically favorable compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Combined immune checkpoint blockade (ICB) using nivolumab and ipilimumab shows significant efficacy in treating advanced melanoma, but it also leads to a higher frequency and severity of adverse drug reactions (ADRs) compared to single-agent therapies, based on pooled safety data from 1551 patients.

Most immune-related ADRs are reversible with glucocorticoids, but due to the increased risk and rapid onset of these toxicities, clinicians must be well-trained to monitor and manage these side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. Hassel, JC., Heinzerling, L., Aberle, J., et al.[2022]

Nivolumab, a monoclonal antibody targeting the programmed death receptor-1, has shown promising efficacy in treating advanced malignant melanoma, with nearly 25% of patients achieving a partial tumor response in a phase II trial involving previously treated stage III/IV patients.

The treatment demonstrated a durable clinical benefit, with a median progression-free survival of 172 days and an acceptable safety profile, as less than 18% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review of its use in patients with malignant melanoma. Deeks, ED.[2021]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

Over 40% of melanoma patients treated with anti-PD-1 therapy experience dermatologic immune-related adverse events (irAEs), but these are typically self-limiting and manageable, with common issues including rashes and itching.

Both anti-PD-1 and anti-PD-L1 antibodies show a similar dermatologic safety profile, and while these skin reactions are frequent, they rarely lead to severe complications or the need to stop treatment, highlighting the importance of early recognition and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. Sibaud, V., Meyer, N., Lamant, L., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

In a phase 1 trial involving 53 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 40% objective response rate, with 65% of patients showing clinical activity, indicating significant effectiveness in tumor reduction.

The concurrent treatment had a manageable safety profile, with 53% of patients experiencing grade 3 or 4 adverse events, which were similar to those seen with monotherapy and generally reversible, suggesting that this combination therapy is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in advanced melanoma. Wolchok, JD., Kluger, H., Callahan, MK., et al.[2022]

Citations

1. targetedonc.com targetedonc.com/view/hbi-8000-plus-nivolumab-is-safe-active-in-melanoma

HBI-8000 Plus Nivolumab Is Safe, Active in Melanoma The combination of HBI-8000 and nivolumab induced a response in nearly two-thirds of patients with advanced melanoma and no prior anti–PD-1/PD-L1 treatment.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04674683

NCT04674683 | Study Comparing Investigational Drug HBI ... This is a clinical study to compare the efficacy and safety of HBI-8000 combined with nivolumab to Placebo combined with nivolumab in patients with ...

3. huyabio.com huyabio.com/huyabio-presents-positive-phase-2-data-on-hbi-8000-and-nivolumab-combination-for-advanced-melanoma/

HUYABIO Presents Positive Phase 2 Data on HBI-8000 ... HBI-8000, an oral drug, when combined with nivolumab has shown encouraging efficacy signals in treating patients with advanced and metastatic melanoma.

4. huyabio.com huyabio.com/huyabio-announces-first-patient-treated-in-a-pivotal-study-of-hbi-8000-combined-with-opdivo-nivolumab-in-patients-with-advanced-melanoma/

HUYABIO Announces First Patient Treated in a Pivotal ... This trial potentially offers a practice-changing, effective combination treatment of HBI-8000 with Opdivo to our patients on the Sunshine Coast ...

5. withpower.com withpower.com/trial/phase-3-melanoma-2021-d1409

HBI-8000 + Nivolumab for Melanoma · Info for Participants Nivolumab, one of the drugs in the combination, has shown promising results in treating advanced melanoma, with patients experiencing durable tumor responses ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04674683

NCT04674683 | Study Comparing Investigational Drug HBI ... This is a clinical study to compare the efficacy and safety of HBI-8000 combined with nivolumab to Placebo combined with nivolumab in patients with ...

7. prnewswire.com prnewswire.com/news-releases/huyabio-presents-positive-phase-2-data-on-hbi-8000-and-nivolumab-combination-for-advanced-melanoma-302300026.html

HUYABIO Presents Positive Phase 2 Data on HBI-8000 ... HBI-8000, an oral drug, when combined with nivolumab has shown encouraging efficacy signals in treating patients with advanced and metastatic melanoma.