Nivolumab + Relatlimab for Advanced Cancer

Recruiting at 1 trial location

Overseen By Colleen Apostal, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: PD-1/PD-L1 inhibitors

Must not be taking: Antineoplastics, Steroids, Cytotoxics, others

Disqualifiers: Brain metastases, Autoimmune disease, Heart disease, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of two drugs, nivolumab (Opdivo) and relatlimab (Opdualag), both immunotherapy drugs, for treating advanced cancer. It targets individuals with solid tumors that exhibit high microsatellite instability, a type of genetic change, and who have not benefited from previous treatments targeting PD-(L)1. Participants will receive varying doses of the drugs to determine the most effective regimen. Ideal candidates have advanced cancer unresponsive to existing treatments and at least one measurable tumor. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 have had chemotherapy, radiation, or steroids within 14 days before starting the study treatment. It's best to discuss your specific medications with the study team.

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

Research has shown that the combination of nivolumab and relatlimab has been tested for safety in people with advanced melanoma, a type of skin cancer. These studies found that the safety profile of this combination is similar to that of nivolumab and relatlimab when used separately, meaning the side effects were expected.

Common side effects included tiredness and skin rash, which are usually manageable. Serious side effects were less common but did occur. While the combination is generally well-tolerated, individual reactions may vary. Prospective trial participants should discuss potential risks with the trial team to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Nivolumab and Relatlimab are unique because they target the immune system in a novel way. Most treatments for advanced cancer focus on directly attacking cancer cells, but these drugs work by enhancing the body's immune response against the cancer. Nivolumab blocks a protein called PD-1 on immune cells, preventing cancer from hiding, while Relatlimab targets LAG-3, another checkpoint that can slow down T-cell activation. This combination may offer a more powerful immune response compared to current standard options like chemotherapy or single-agent immunotherapies. Researchers are excited because this approach could lead to better control of the cancer and potentially improve survival rates.

What evidence suggests that nivolumab and relatlimab could be effective for advanced cancer?

Research has shown that using nivolumab and relatlimab together can help treat some advanced cancers. In this trial, participants will receive different dosages of the nivolumab and relatlimab combination. In patients with advanced melanoma, those on this combination treatment had their cancer remain stable for twice as long compared to those on standard treatments. Studies also show that this drug pair consistently improves progression-free survival, meaning the time a patient lives with the disease without it worsening. This suggests that the treatment might manage cancer more effectively than some other options, especially for cases that haven't responded well to previous treatments. ^{5 6 7 8 9}

Who Is on the Research Team?

Dung Le, MD

Principal Investigator

Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

Adults with advanced cancers that have high microsatellite instability and didn't respond to previous PD-1/PD-L1 inhibitor therapy. Participants must be in good physical condition, have at least one measurable lesion, proper organ and marrow function, no severe allergies to monoclonal antibodies or history of certain diseases like interstitial lung disease or brain metastases.

Inclusion Criteria

I am fully active or can carry out light work.

My organ and bone marrow functions meet the study's requirements.

My heart's pumping ability is normal.

Exclusion Criteria

I currently have an active infection.

I have or had cancer spread to my brain.

Had any investigational cytotoxic drug within 4 weeks prior to study treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab and relatlimab in various dosing regimens for advanced mismatch repair deficient cancers

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Relatlimab

Trial Overview The trial is testing the combination of Nivolumab and Relatlimab for effectiveness and safety in patients whose tumors are resistant to prior therapies targeting PD-(L)1 proteins. It aims to see if this new treatment can help control cancer growth.

How Is the Trial Designed?

Group I: Cohort 3: Nivolumab and Relatlimab Experimental Treatment 2 Interventions

480mg/480mg (sequential administration)

Group II: Cohort 2: Nivolumab and Relatlimab Experimental Treatment 2 Interventions

480mg/960mg or 480mg/160mg (sequential administration)

Group III: Cohort 1: Nivolumab and Relatlimab Experimental Treatment 2 Interventions

480mg/160mg (co-administered)

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nivolumab plus relatlimab is a combination immunotherapy that targets immune checkpoints, specifically PD-1 and LAG-3, and has been approved for treating unresectable or metastatic melanoma in adults and adolescents weighing at least 40 kg.

This combination therapy represents a significant advancement in cancer treatment, as it utilizes two different mechanisms to enhance the immune response against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. Paik, J.[2022]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

In a study of 129 patients with advanced melanoma treated with nivolumab and relatlimab, those without diabetes had significantly better progression-free survival (PFS) and overall survival (OS) compared to patients with type 2 diabetes, indicating that diabetes negatively impacts treatment efficacy.

Interestingly, patients who developed immune checkpoint inhibitor-induced diabetes (ICI-DM) during treatment had the best outcomes, suggesting that this condition may enhance the effectiveness of the therapy, possibly due to changes in LAG3 expression in tumor tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab. Mallardo, D., Woodford, R., Menzies, AM., et al.[2023]

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 and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

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 (Opdivo) is an effective immune checkpoint inhibitor that enhances the immune system's ability to fight advanced cancers, showing impressive durability of response compared to traditional therapies.

It is well tolerated and approved for several types of cancer, including non-small cell lung cancer, melanoma, and renal cell carcinoma, with ongoing research to identify biomarkers for response and explore combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab, anti-programmed death-1 (PD-1) monoclonal antibody immunotherapy: Role in advanced cancers. Rajan, A., Kim, C., Heery, CR., et al.[2023]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Citations

1. opdualag.com opdualag.com/about/results

Advanced Melanoma Clinical Trial Results Half the patients on Opdualag went 2X longer without advanced melanoma worsening than those on a standard treatment. In a clinical trial of 714 patients ...

2. opdualaghcp.com opdualaghcp.com/efficacy/melanoma/relativity-047

Efficacy | Opdualag® (nivolumab and relatlimab-rmbw) for HCPs All data shown below is 4-year data based on minimum potential follow-up of 45.3 months.2. Overall survival at 4 years ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10164023/

The Latest Option: Nivolumab and Relatlimab in Advanced ... Based on the results of two phase 2 trials the combination therapy with ipilimumab and nivolumab lead to an ORR of up to 56% intracranially in patients with ...

4. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Provides-Update-on-Phase-3-RELATIVITY-098-Trial/default.aspx

Bristol Myers Squibb Provides Update on Phase 3 ... RELATIVITY-098 is a randomized Phase 3, double-blind study evaluating adjuvant immunotherapy with Opdualag, the fixed-dose combination of nivolumab and ...

5. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2200239

Overall Survival and Response with Nivolumab and ... The fixed-dose combination of nivolumab + relatlimab showed consistent PFS benefit versus nivolumab with approximately 6 months of additional median follow-up.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07079644

Outcomes of Nivolumab in Combination With Relatlimab ... Real World Outcomes of Nivolumab + Relatlimab in Patients With Advanced Melanoma in the Flatiron Database. Conditions. Advanced Melanoma. Advanced Melanoma.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.01124

Three-Year Overall Survival With Nivolumab Plus ... Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically meaningful, but not ...

8. nature.com nature.com/articles/s41591-025-04032-8

Adjuvant nivolumab and relatlimab in stage III/IV melanoma Clinical results presented in this report show that there was no added benefit in the resected setting for nivolumab plus relatlimab over ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK604840/

Clinical Review - Nivolumab and Relatlimab (Opdualag) - NCBI The objective of the safety outcomes was to assess the overall safety and tolerability of nivolumab-relatlimab and nivolumab. Safety data reported in this ...