Nivolumab for Melanoma Prevention

(CheckMate76K Trial)

Not currently recruiting at 321 trial locations

Overseen By Recruiting sites have contact information. Please contact the sites directly. If there is no contact information,

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Ocular melanoma, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 13 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nivolumab, an immunotherapy drug, can help prevent melanoma from returning after surgery. The study compares nivolumab to a placebo (a harmless pill with no active ingredients) to determine which is more effective. It targets individuals who have had Stage IIB or IIC melanoma surgically removed, show no current signs of the disease, but are at high risk of recurrence. Those who have not undergone melanoma treatment before and had a negative sentinel lymph node biopsy (a test to check for cancer spread) might be suitable candidates. 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 information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that nivolumab is generally well-tolerated by people with melanoma. In studies, patients taking nivolumab have shown high survival rates. For example, one study found that 85% of patients treated with nivolumab were still alive after ten years. This suggests that nivolumab is effective and safe for many people. However, its safety and effectiveness for children under 12 years old remain unclear. Most side effects in adults are manageable and can include tiredness, skin rash, and nausea. Always consult a healthcare provider to determine if this treatment is appropriate. ^{1 2 3 4 5}

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

Unlike standard treatments for melanoma, such as surgery, chemotherapy, and radiation, Nivolumab works by harnessing the power of the immune system. It is a type of immunotherapy known as a checkpoint inhibitor, which specifically targets and blocks the PD-1 pathway. This action boosts the immune response against melanoma cells, potentially preventing the disease before it can take hold. Researchers are particularly excited about its potential for effectiveness in melanoma prevention, offering a new strategy that could complement or even surpass existing treatment options.

What evidence suggests that nivolumab might be an effective treatment for melanoma?

Studies have shown that nivolumab effectively treats melanoma, a type of skin cancer. In patients with melanoma, this drug has been linked to high survival rates. For example, those treated with nivolumab have an 85% chance of surviving for 10 years, which is significant. Nivolumab enhances the immune system's ability to fight cancer cells. In this trial, some participants will receive nivolumab to evaluate its potential in preventing melanoma recurrence after surgery. These findings suggest that nivolumab could benefit individuals at high risk of melanoma returning post-surgery. ^{1 3 4 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults and kids who've had surgery to remove Stage IIB/C melanoma and are at high risk of it coming back. They should be in good physical shape (ECOG 0 or 1), have not been treated for melanoma before, and can't be pregnant or nursing. People with a history of certain types of melanoma, autoimmune diseases, allergies to the drug's ingredients, or previous treatments targeting immune checkpoints cannot join.

Inclusion Criteria

I am fully active or can carry out light work.

I was diagnosed with Stage IIB/C melanoma that was surgically removed.

I have never been treated for melanoma.

Exclusion Criteria

I have been treated with specific immune system targeting drugs before.

You have a known or suspected ongoing autoimmune disease.

Known history of allergy or hypersensitivity to study drug components

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab or placebo after complete resection of Stage IIB/C melanoma

13 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

32 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Placebo

Trial Overview The study is testing if Nivolumab, an immunotherapy drug, can prevent melanoma from returning after surgery better than a placebo (a treatment with no active drug). Participants will randomly receive either Nivolumab or the placebo to compare their effectiveness.

How Is the Trial Designed?

Group I: Nivolumab Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead 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, 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]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

In a study of 88 patients with metastatic melanoma, higher serum concentrations of nivolumab were significantly correlated with better clinical outcomes, including overall and progression-free survival.

Patients who achieved a clinical response not only had higher nivolumab levels but also exhibited a distinct genetic profile with increased activation of genes related to T-cell activation, suggesting that both drug concentration and genetic factors may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis. Mallardo, D., Giannarelli, D., Vitale, MG., et al.[2023]

Ipilimumab, a first-in-class T-cell potentiator, has shown significant improvements in overall survival for advanced melanoma patients in a phase 3 trial, with median survival extending to 10.1 months compared to 6.4 months for the control group.

The treatment demonstrated long-term survival benefits, with 24-month survival rates increasing from 13.7% with the gp100 vaccine alone to 21.6% and 23.5% for patients receiving ipilimumab alone or in combination, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. Tarhini, A., Lo, E., Minor, DR.[2021]

Nivolumab (OPDIVO) received accelerated FDA approval for treating unresectable or metastatic melanoma based on a 31.7% objective response rate in a study of 120 patients, showing promising efficacy after prior treatments.

The treatment demonstrated durable responses, with 87% of responding patients maintaining their response for at least 6 months, although it carries risks of immune-mediated adverse reactions that were monitored in a safety assessment of 268 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. Hazarika, M., Chuk, MK., Theoret, MR., et al.[2023]

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 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]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab significantly improves recurrence-free survival (RFS) and overall survival (OS) in patients with high-risk resected melanoma compared to a watch-and-wait strategy, with hazard ratios of 0.53 and 0.63, respectively.

In patients with stage IIIB/IIIC melanoma, nivolumab also shows meaningful improvements in distant metastasis-free survival (DMFS) and OS, indicating its effectiveness across different stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma. Weber, JS., Ascierto, PA., Middleton, MR., et al.[2021]

The combination of nivolumab and relatlimab shows a manageable safety profile for patients with advanced melanoma who have already undergone treatment.

This combination therapy may offer a new option for patients with pretreated melanoma, suggesting potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

In a study of 37 patients with stage IV metastatic melanoma, high levels of soluble CD73 (sCD73) enzyme activity in the serum were linked to significantly poorer overall survival and progression-free survival when treated with nivolumab.

Patients with high sCD73 activity had a median progression-free survival of only 2.6 months compared to 14.2 months for those with lower activity, suggesting that measuring sCD73 could help predict how well patients will respond to nivolumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. Morello, S., Capone, M., Sorrentino, C., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12080919/

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in ... Among these patients, 10-year overall survival rates were 86% with nivolumab-plus-ipilimumab, 85% with nivolumab, and 79% with ipilimumab ( ...

2. opdivohcp.com opdivohcp.com/efficacy/melanoma

Efficacy Data for Melanoma | OPDIVO® (nivolumab) In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC ...

3. news.bms.com news.bms.com/news/details/2021/Six-and-a-Half-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Continue-to-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Six-and-a-Half-Year Outcomes for Opdivo (nivolumab) in ... Data evaluating Opdivo plus Yervoy represent the longest reported median overall survival from a Phase 3 advanced melanoma trial.

4. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2407417

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab ... Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97 ...

5. opdivo.com opdivo.com/melanoma/clinical-trial-results/advanced-immunotherapy-combination

Advanced Melanoma Skin Cancer | Clinical Trial Results OPDIVO + YERVOY is FDA approved to treat advanced melanoma regardless of your test results. More people given OPDIVO + YERVOY were alive compared to YERVOY ...

6. opdivo.com opdivo.com/melanoma/clinical-trial-results

Melanoma Skin Cancer | Clinical Trial Results It is not known if OPDIVO is safe and effective in children younger than 12 years of age with melanoma or MSI-H or dMMR metastatic colorectal cancer. It is not ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00400

Pooled Long-Term Outcomes With Nivolumab Plus ... In this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment–naïve ...