Nivolumab for Melanoma Prevention

(CheckMate76K Trial)

Recruiting at 299 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

790 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing if nivolumab can help prevent melanoma from returning in patients who have had their cancer surgically removed but are at high risk for it coming back. Nivolumab boosts the immune system to fight any remaining cancer cells. Nivolumab is used for the treatment of malignant melanoma and has shown promising anticancer activity in various cancers.

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 Nivolumab safe for humans?

Nivolumab has been shown to have a manageable safety profile in patients with melanoma, but it can cause immune-related side effects like fatigue, diarrhea, and rash. There have also been reports of hepatitis B reactivation in some patients using similar treatments. ^{1 2 3 4 5}

How does the drug nivolumab differ from other treatments for melanoma?

Nivolumab is unique because it is an immune checkpoint inhibitor that targets the programmed death-1 (PD-1) pathway, helping the immune system attack melanoma cells. Unlike traditional chemotherapy, it is administered intravenously and has shown improved survival rates in patients with unresectable or metastatic melanoma. ^{3 6 7 8 9}

What evidence supports the effectiveness of the drug Nivolumab for preventing melanoma?

Research shows that Nivolumab, an immune checkpoint inhibitor, has demonstrated long-term survival benefits in patients with advanced melanoma and is used as a standard adjuvant therapy for high-risk resected melanoma, suggesting its potential effectiveness in melanoma prevention. ^{6 7 10 11 12}

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

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]

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 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]

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]

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]

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]

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]

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]

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, 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, 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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

Nivolumab versus placebo as adjuvant therapy for resected stage III melanoma: a propensity weighted indirect treatment comparison and number needed to treat analysis for recurrence-free survival and overall survival. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]

9. England 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. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

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

12. New Zealand pubmed.ncbi.nlm.nih.gov

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