Relatlimab + Nivolumab for Recurrent Glioblastoma

Recruiting at 263 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Anti-PD1 agents

Disqualifiers: Active brain metastases, Autoimmune disorders, 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: 6

Duration: Up to 30 months

184 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for glioblastoma, a type of brain cancer that has returned after initial improvement. Researchers compare two immunotherapy drugs, relatlimab and nivolumab, which aim to help the immune system fight the cancer, against lomustine, a standard chemotherapy drug. Participants should have glioblastoma that has recurred after previous treatments like surgery, radiation, and temozolomide. The research aims to determine if the new drug combination is safer or more effective than current standard treatments. As a Phase 2 trial, it focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The protocol does not specify if you need to stop taking your current medications. However, you must be off corticosteroids for at least 5 days before joining the trial.

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

Research has shown that using relatlimab with nivolumab is about as safe as using nivolumab alone. Nivolumab is a well-known treatment that helps the immune system fight cancer, suggesting that the combination is generally well-tolerated.

In other studies, patients who took both relatlimab and nivolumab reported side effects similar to those from nivolumab alone. Common side effects include fatigue and skin reactions, typical for treatments that boost the immune system.

Although specific safety data for this combination in treating recurrent glioblastoma is not yet available, its safety in other conditions is reassuring. Since this trial is in Phase 2, earlier studies have provided enough evidence of safety to continue testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Relatlimab and Nivolumab for treating recurrent glioblastoma because these drugs work together to target and inhibit immune checkpoints, which can enhance the body's immune response against cancer cells. Unlike traditional chemotherapy options like temozolomide or lomustine, which attack cancer cells directly, this combination boosts the immune system's ability to recognize and destroy these cells. Relatlimab specifically targets the LAG-3 protein on immune cells, while Nivolumab targets the PD-1 pathway, making them a novel duo in the fight against this aggressive brain cancer. This approach has the potential to provide a more targeted and effective treatment, reducing the rate of cancer progression with possibly fewer side effects compared to conventional therapies.

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

Research has shown that the combination of two drugs, relatlimab and nivolumab, which participants in this trial may receive, might help treat recurrent glioblastoma. These drugs are monoclonal antibodies that assist the immune system in identifying and fighting cancer cells. Early results suggest that this combination can slow cancer cell growth. Studies indicate that this type of treatment, known as immunotherapy, may enhance the immune system's ability to attack tumors. Although more information is needed, the initial findings are promising for patients with recurrent glioblastoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Michael Lim

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent glioblastoma, confirmed by WHO criteria and RANO criteria. Participants must have stable neurological status without steroids for 5 days, a Karnofsky Performance Status of at least 60%, an ALC of ≥1000/mm^3, no IDH mutation, and are in their first recurrence post radiation therapy and temozolomide. Prior treatments should be completed within specific time frames before joining.

Inclusion Criteria

I haven't taken corticosteroids for 5 days before signing up.

Absolute lymphocyte count (ALC): ≥ 1000/mm^3

Platelet count: ≥ 100,000/mm^3

Exclusion Criteria

I do not have any lung problems causing symptoms.

I do not have any autoimmune diseases needing treatment, except possibly thyroid issues or diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either nivolumab and relatlimab intravenously or lomustine orally, with cycles repeating every 28 or 42 days respectively, in the absence of disease progression or unacceptable toxicity.

Up to 30 months

Monthly visits for IV administration or every 6 weeks for oral administration

Follow-up

Participants are monitored for overall survival and adverse events every 6 months for up to 5 years after treatment completion.

Up to 5 years

Biannual visits

What Are the Treatments Tested in This Trial?

Interventions

• Lomustine
• Nivolumab
• Relatlimab

Trial Overview The trial compares the safety and effectiveness of two monoclonal antibodies (Relatlimab & Nivolumab) against standard chemotherapy drug Lomustine in patients with recurrent glioblastoma. It aims to see if these antibodies can better inhibit tumor growth compared to traditional treatment.

How Is the Trial Designed?

Group I: Arm I (nivolumab, relatlimab) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 30 minutes followed by relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.

Group II: Arm II (lomustine) Active Control 5 Interventions

Patients receive lomustine PO on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 40 newly diagnosed and 86 recurrent glioblastoma patients, PD-L1 blockade with durvalumab did not meet primary efficacy endpoints, indicating it was ineffective in improving outcomes compared to standard treatments.

Recurrent glioblastoma patients exhibited significantly lower levels of circulating immune cell subsets, and the use of dexamethasone was associated with a reduction in these immune cells, suggesting that immune suppression may hinder treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma. Nayak, L., Standifer, N., Dietrich, J., et al.[2023]

Intracerebral administration of ipilimumab (IPI) and nivolumab (NIVO) after maximal safe resection of recurrent glioblastoma (rGB) was found to be feasible and safe, with mild immune-related adverse events and no significant central nervous system toxicity observed.

The treatment resulted in a median overall survival of 38 weeks, which is favorable compared to historical data, suggesting that this approach may improve outcomes for patients with rGB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial. Duerinck, J., Schwarze, JK., Awada, G., et al.[2022]

In a study of 31 adult patients with recurrent high-grade gliomas, salvage therapy using PD-1-blocking antibodies nivolumab or pembrolizumab, with or without bevacizumab, showed a median progression-free survival of only 3.2 months, indicating limited efficacy.

The study found no significant survival benefit from these treatments in this patient population, suggesting that PD-1-blocking antibodies should be used cautiously and only in selected cases until further clinical trial results are available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma. Kurz, SC., Cabrera, LP., Hastie, D., et al.[2019]

Nivolumab treatment showed improved overall survival outcomes in patients with newly diagnosed glioblastoma multiforme (GBM), indicating potential efficacy for this group.

However, Nivolumab did not demonstrate significant benefits in progression-free survival or in patients with recurrent GBM, suggesting that its effectiveness may be limited to newly diagnosed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for newly and recurrent glioblastoma multiforme treatment: A systematic review and meta-analysis. Araujo Moura, AW., da Silva Rodrigues, S., de Oliveira, TF., 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]

A systematic review of 48 randomized trials for recurrent glioblastoma (rGBM) found that there is no single systemic therapy that shows a clear survival advantage, with median overall survival ranging from 3 to 17.6 months across studies.

The inconsistency in outcome reporting among studies made it difficult to perform a network meta-analysis, highlighting the need for standardized measures in future research on rGBM treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current landscape of systemic therapy for recurrent glioblastoma: A systematic review of randomized-controlled trials. Fazzari, FGT., Rose, F., Pauls, M., et al.[2022]

Nivolumab alone was better tolerated than when combined with ipilimumab, with treatment-related adverse events like fatigue and diarrhea being more common in the combination therapy group.

Despite the safety concerns, some patients showed promising responses, with three achieving partial responses and eight maintaining stable disease for at least 12 weeks, indicating potential efficacy of nivolumab in treating recurrent glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Omuro, A., Vlahovic, G., Lim, M., et al.[2023]

In a study of 26 patients with recurrent glioblastoma, pembrolizumab showed an overall response rate of 8%, with two patients experiencing partial responses lasting up to 22.8 months, indicating some durable antitumor activity.

While 73% of patients experienced treatment-related adverse events, most were manageable, suggesting that pembrolizumab has a safety profile that allows for further exploration in combination therapies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Reardon, DA., Kim, TM., Frenel, JS., et al.[2021]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06325683

Study Details | NCT06325683 | Anti-Lag-3 (Relatlimab ... Giving relatlimab and nivolumab may be safe, tolerable, and/or effective compared to standard of care lomustine in treating patients with recurrent glioblastoma ...

3. withpower.com withpower.com/trial/phase-2-glioblastoma-5-2024-ed760

Relatlimab + Nivolumab for Recurrent Glioblastoma This phase II trial compares the safety, side effects and effectiveness of anti-lag-3 (relatlimab) and anti-PD-1 blockade (nivolumab) to standard of care ...

4. curetoday.com curetoday.com/view/clinical-trial-to-evaluate-opdivo-opdualag-in-glioblastoma

Clinical Trial to Evaluate Opdivo, Opdualag in Glioblastoma The phase 2 GIANT trial will evaluate Opdivo with or without relatlimab in IDH-wildtype newly diagnosed glioblastoma.

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11427296/

Immune checkpoint pathways in glioblastoma - PubMed Central A phase I trial exploring the safety of relatlimab or urelumab (anti-CD137) alone or in combination with nivolumab in recurrent glioblastoma was completed in ...

7. ono-pharma.com ono-pharma.com/sites/default/files/en/news/press/sm_cn170605_3.pdf

Anti-LAG-3 (BMS-986016) in Combination with Opdivo ( ... Combination of two checkpoint inhibitors had a similar safety profile to Opdivo monotherapy. (PRINCETON, N.J., June 3, 2017) – Bristol-Myers ...