Subcutaneous vs Intravenous Nivolumab + Relatlimab for Melanoma

Not currently recruiting at 66 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Steroids, Immunosuppressive drugs

Disqualifiers: Brain cancer, Eye cancer, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how people with melanoma (a type of skin cancer) feel about receiving their medication through a subcutaneous shot compared to an intravenous (IV) method. It also assesses the safety of switching from IV to the subcutaneous method. The trial seeks participants with either advanced melanoma or those who have had surgery to remove melanoma and are now cancer-free. Participants should not have certain other health conditions, such as brain cancer or autoimmune diseases. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking steroids or immunosuppressive drugs.

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

Research has shown that nivolumab, administered either as an injection under the skin or directly into a vein, has a well-established safety record for treating melanoma, a type of skin cancer. In earlier studies, 42% of patients taking nivolumab reported serious side effects, with the most severe occurring in 2% to less than 5% of these patients.

The safety profile of nivolumab given under the skin is similar to when it is administered into a vein, with side effects occurring at comparable frequencies and severities. Additionally, the FDA has approved nivolumab as a safe and effective treatment for melanoma, reinforcing its safety record.

Overall, while serious side effects can occur, they align with previous findings, and nivolumab remains a common treatment for melanoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Nivolumab combined with Relatlimab is unique because it offers a new way to treat melanoma by using a different delivery method—subcutaneous injection, as opposed to the more common intravenous administration. This can make treatment more convenient and accessible for patients since it might be done outside of a hospital setting. Researchers are excited because this combination uses a dual immune checkpoint blockade, meaning it targets two different pathways that tumors use to evade the immune system. This approach could potentially enhance the body's ability to fight the melanoma more effectively than existing options.

What evidence suggests that this trial's treatments could be effective for melanoma?

Research has shown that nivolumab effectively treats melanoma, a type of skin cancer. Studies have found that nivolumab, when used alone, significantly improves survival rates. For instance, in a clinical trial with patients who had advanced melanoma and had not been treated before, those who received nivolumab showed promising results. In this trial, participants will receive nivolumab either as an injection under the skin or intravenously. Specifically, previous studies demonstrated that when nivolumab was given as an injection under the skin, 24% of patients experienced tumor shrinkage or disappearance. Overall, nivolumab shows strong potential in improving the lives of people with melanoma. ^{4 6 7 8 9}

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 with melanoma, either metastatic without prior treatment or resected and confirmed disease-free within the last 12 weeks. Participants should have low disability and be at intermediate to advanced risk. Those with brain cancer treated by radiation, eye/mucous membrane cancers, autoimmune diseases, or on steroids/immunosuppressants cannot join.

Inclusion Criteria

I have melanoma that is either untreated and metastatic, or was fully removed by surgery within the last 12 weeks and I am currently cancer-free.

My melanoma is advanced or at risk of becoming advanced, but I have low disability.

Exclusion Criteria

You do not have any autoimmune disease.

I am not currently taking steroids for inflammation or drugs that weaken my immune system.

I do not have cancer in my eyes or mucous membranes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nivolumab subcutaneous or nivolumab + relatlimab fixed-dose combination subcutaneous, and switch from intravenous to subcutaneous administration

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview The study evaluates patient preference between subcutaneous (under the skin) injections versus intravenous (into a vein) administration of Nivolumab alone or combined with Relatlimab. It also examines safety related to switching from IV to SC delivery.

How Is the Trial Designed?

Group I: Cohort 2: Resected Melanoma Experimental Treatment 2 Interventions

Group II: Cohort 1: Metastatic Melanoma Experimental Treatment 2 Interventions

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 355 patients with metastatic melanoma resistant to anti-PD-(L)1 therapy, combining ipilimumab with anti-PD-1 (either pembrolizumab or nivolumab) resulted in a significantly higher objective response rate (31%) compared to ipilimumab alone (13%).

Patients receiving the combination therapy also experienced longer overall survival (20.4 months vs. 8.8 months) and longer progression-free survival (3.0 months vs. 2.6 months), while the rates of severe adverse events were similar between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study. Pires da Silva, I., Ahmed, T., Reijers, ILM., et al.[2021]

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]

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]

Nivolumab, either alone or in combination with ipilimumab, significantly improves response rates in patients with advanced unresectable melanoma compared to ipilimumab alone, with a relative risk of 3.58 for objective response rates and 5.93 for complete response rates based on a review of four randomized-controlled trials involving 1910 patients.

Nivolumab also offers longer progression-free survival compared to ipilimumab alone, while maintaining a comparable safety profile, indicating its efficacy as a first-line treatment option for advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab monotherapy or in combination with ipilimumab for metastatic melanoma: systematic review and meta-analysis of randomized-controlled trials. Menshawy, A., Eltonob, AA., Barkat, SA., et al.[2023]

In a phase 3 trial with patients suffering from advanced melanoma, the combination of nivolumab and ipilimumab resulted in significantly longer overall survival rates (58% at 3 years) compared to ipilimumab alone (34%).

The safety profile of the combination therapy was consistent with previous reports, showing that 59% of patients experienced severe treatment-related adverse events, indicating that while effective, the combination therapy has a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. Wolchok, JD., Chiarion-Sileni, V., Gonzalez, R., 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 (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]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

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]

Citations

1. opdivo.com opdivo.com/melanoma/clinical-trial-results/advanced-immunotherapy

Advanced Melanoma Skin Cancer | Clinical Trial Results In a clinical trial of 945 people with previously untreated advanced melanoma, 314 people were given OPDIVO + YERVOY, 316 people were given OPDIVO alone, and ...

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/2024/Bristol-Myers-Squibb-Presents-Landmark-10-Year-Follow-Up-Data-from-CheckMate--067-Which-Showed-Continued-Durable-Long-Term-Survival-Benefit-with-Opdivo-plus-Yervoy-in-Advanced-Melanoma/default.aspx

067 Which Showed Continued Durable Long-Term ... With a minimum follow up of 10 years, median overall survival (OS) was 71.9 months with Opdivo plus Yervoy (95% CI: 38.2-114.4) - the longest ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4346215/

Nivolumab in melanoma: latest evidence and clinical potential These data were recently updated at the American Society of Clinical Oncology (ASCO) annual meeting in 2014 and demonstrated a 48% survival rate at 2 years and ...

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. opdivohcp.com opdivohcp.com/safety/melanoma

Safety Profile for Melanoma | OPDIVO® (nivolumab) In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34452930/

Adjuvant nivolumab for stage III/IV melanoma: evaluation of ... Conclusion: Results of this safety analysis of nivolumab in adjuvant melanoma were consistent with its established safety profile. In the discrete time ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9939122/

Real‐World nivolumab dosing patterns and safety outcomes ... Nivolumab at a dose of 480 mg every 4 weeks (Q4W) is approved for the adjuvant treatment of melanoma. However, real‐world data on this regimen are limited ...

9. news.bms.com news.bms.com/news/details/2019/Five-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Five-Year Outcomes for Opdivo (nivolumab) in ... Five-year overall survival rates were 52% for the Opdivo plus Yervoy combination, 44% for Opdivo alone, and 26% for Yervoy alone.