Nivolumab + Relatlimab vs Pembrolizumab with Chemotherapy for Lung Cancer

(RELATIVITY1093 Trial)

Recruiting at 483 trial locations

Overseen By BMS Study Connect www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Targeted inhibitors, Immunotherapy

Disqualifiers: Pregnancy, CNS metastases, Autoimmune, others

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

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: 12 weeks

1000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatment options for people with advanced non-small cell lung cancer. Researchers aim to determine if combining Nivolumab (Opdivo) and Relatlimab with chemotherapy is more effective than Pembrolizumab (KEYTRUDA) with chemotherapy. The trial seeks participants with stage IV or recurrent non-small cell lung cancer who have not received prior treatment for advanced disease. Participants should also have a specific marker, PD-L1, present in their tumor cells. 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 has shown that using Nivolumab and Relatlimab together is generally safe, based on existing knowledge of these drugs. In studies, over 15% of patients experienced common side effects, but no new safety concerns emerged over four years. However, this combination may cause more serious side effects than Nivolumab alone.

The safety of Pembrolizumab is well-established, as it is already used for other conditions. Most people tolerate it well, though some may experience fatigue or nausea.

Overall, both treatment options in this trial have been studied before. They are usually well-tolerated, but there is always a chance of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and Relatlimab for lung cancer because it targets the immune system in a unique way. Unlike traditional treatments like Pembrolizumab with chemotherapy, which usually focus on one checkpoint inhibitor, this combination uses two. Nivolumab blocks the PD-1 pathway, while Relatlimab targets the LAG-3 pathway, potentially offering a more powerful immune response against the cancer. This dual action could lead to better outcomes for patients by enhancing the body’s ability to recognize and attack cancer cells.

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

This trial will compare two treatment approaches for lung cancer. Research has shown that combining Nivolumab and Relatlimab, which participants in Arm A of this trial may receive, may help treat lung cancer. One study found that adding Relatlimab to Nivolumab and chemotherapy improved outcomes for patients with stage IV non-small cell lung cancer, helping them live longer without their cancer worsening.

Meanwhile, Pembrolizumab with chemotherapy, which participants in Arm B of this trial may receive, is already known to work well for this type of lung cancer. It has been widely used and has shown significant benefits in extending patients' lives and slowing disease progression. Both treatments are effective, but the ongoing study aims to determine if Nivolumab and Relatlimab might offer additional benefits. ^{2 4 6 7 8}

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 stage IV or recurrent non-squamous non-small cell lung cancer showing PD-L1 levels between 1-49%. Participants should not have had prior systemic treatment for their advanced disease.

Inclusion Criteria

I haven't received any systemic anti-cancer treatments for advanced or metastatic disease.

My cancer can be measured on scans.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have no other cancers needing treatment or active in the last 2 years.

I do not have untreated brain metastases.

I have never had myocarditis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Nivolumab and Relatlimab in combination with chemotherapy or Pembrolizumab with chemotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Pembrolizumab
• Relatlimab

Trial Overview The study aims to compare the effectiveness of two treatments: Nivolumab and Relatlimab combined with chemotherapy versus Pembrolizumab with chemotherapy, in patients matching the specific cancer criteria.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 5 Interventions

Group II: Arm B Active Control 4 Interventions

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?

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, 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 and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

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]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

In a study involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[2023]

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In the KEYNOTE-189 study, first-line treatment with pembrolizumab combined with pemetrexed-platinum significantly improved overall survival (OS) to a median of 22.0 months compared to 10.7 months for the placebo group, indicating a strong efficacy in treating metastatic nonsquamous non-small-cell lung cancer (NSCLC).

The combination therapy also resulted in a median progression-free survival (PFS) of 9.0 months versus 4.9 months for placebo, with benefits observed regardless of tumor PD-L1 expression or the presence of liver/brain metastases, while maintaining a similar incidence of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. Gadgeel, S., Rodríguez-Abreu, D., Speranza, G., et al.[2021]

In a meta-analysis of 15 studies involving cancer patients treated with either nivolumab or pembrolizumab, nivolumab was associated with a higher overall incidence of cardiotoxicity (55.7%) compared to pembrolizumab (27.31%), although this difference was not statistically significant.

However, when looking specifically at myocarditis, pembrolizumab showed a significant increase in cardiotoxicity risk, suggesting that while nivolumab may be more commonly reported for general cardiotoxicity, pembrolizumab poses a greater risk for this specific heart condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. Ndjana Lessomo, FY., Wang, Z., Mukuka, C.[2023]

In a real-life study of 108 patients with advanced non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score of ≥50%, pembrolizumab showed a median progression-free survival of 10.1 months, similar to results from the KEYNOTE-024 trial.

The treatment was generally well-tolerated, with only 8% of patients experiencing grade 3 adverse events, and no severe (grade 4 or 5) adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. Amrane, K., Geier, M., Corre, R., et al.[2021]

Citations

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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 ...

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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 ( ...

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Relatlimab Plus Nivolumab and Chemo Improves Clinical ... Findings from the phase 2 RELATIVITY-104 study demonstrates a clinical benefit with the addition of relatlimab to nivolumab and chemotherapy.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04623775

NCT04623775 | A Study of Relatlimab Plus Nivolumab in ... The purpose of this study is to assess the safety profile of relatlimab plus nivolumab in combination with platinum doublet chemotherapy (PDCT) and to ...

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. opdualaghcp.com opdualaghcp.com/safety/melanoma/relativity-047

Safety Profile - Opdualag® (nivolumab and relatlimab-rmbw) Adverse reactions occurring in ≥15% of patients in the Opdualag or nivolumab monotherapy arm1. No new or unexpected safety events with 4-year data3.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299925007459

Safety profile of nivolumab-relatlimab in cancer patients Compared with nivolumab monotherapy, therapy with nivolumab-relatlimab was associated with a significantly increased risk of high-grade TRAEs, and some ...

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Advanced Melanoma Treatment | Opdualag® (nivolumab and ... It is not known if Opdualag is safe and effective when used in children younger than 12 years of age or in children 12 years and older weighing less than 88 ...