Subcutaneous vs Intravenous Nivolumab + Relatlimab for Melanoma

Recruiting at 62 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

100 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Nivolumab for melanoma?

Research shows that Nivolumab, when used alone or in combination with other drugs like ipilimumab, significantly improves survival rates and slows disease progression in patients with advanced melanoma compared to other treatments. It has been approved by the FDA for treating certain types of melanoma, demonstrating its effectiveness. ^{1 2 3 4 5}

Is Nivolumab plus Relatlimab safe for treating melanoma?

Nivolumab, also known as Opdivo, has been used safely in humans for treating melanoma, with common side effects including tiredness, diarrhea, constipation, nausea, muscle pain, rash, and itching. Nivolumab combined with Relatlimab has a manageable safety profile in patients with advanced melanoma. ^{2 6 7 8 9}

How does the drug Nivolumab + Relatlimab differ from other melanoma treatments?

This treatment is unique because it combines Nivolumab, an immune checkpoint inhibitor, with Relatlimab, and is administered subcutaneously (under the skin) rather than intravenously (into a vein), which may offer more convenience and potentially different side effect profiles compared to traditional intravenous administration. ^{4 5 10 11 12}

What is the purpose of this trial?

This trial is testing two injection methods for cancer treatment to see which one patients prefer and to ensure they are safe. The treatments help the immune system attack cancer cells.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

References

1. England 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. [2022]

2. 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]

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

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. [2023]

4. India pubmed.ncbi.nlm.nih.gov

The efficacy and safety of combined ipilimumab and nivolumab versus ipilimumab in patients with Stage III/IV unresectable melanoma: A systematic review and meta-analysis. [2022]

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

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

Nivolumab monotherapy or in combination with ipilimumab for metastatic melanoma: systematic review and meta-analysis of randomized-controlled trials. [2023]

8. 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]

9. England 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. [2021]

10. Georgia (Republic) 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)]. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Nivolumab in melanoma. [2018]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Early Response Assessment in Advanced Stage Melanoma Treated with Combination Ipilimumab/Nivolumab. [2022]