Trial Summary
What is the purpose of this trial?To learn if giving nivolumab in combination with relatlimab can help to control melanoma that has spread to the brain (melanoma with brain metastases). The safety and side effects of the study drug combination will also be studied.
Is the drug combination of Nivolumab and Relatlimab promising for treating melanoma brain metastases?Yes, the drug combination of Nivolumab and Relatlimab is promising for treating melanoma brain metastases. It has been approved in the USA for treating advanced melanoma, showing that it can effectively target and help the immune system fight cancer cells.79101112
What data supports the idea that Nivolumab + Relatlimab for Melanoma Brain Metastases is an effective drug?The available research shows that the combination of nivolumab and ipilimumab, another similar treatment, provided a 55% response rate in patients with melanoma brain metastases. Additionally, the use of checkpoint blockade immunotherapies, which include drugs like nivolumab, has significantly improved survival rates for patients with melanoma brain metastases. For example, after the approval of these therapies, the 4-year survival rate increased from 7.4% to 14.1%. This suggests that nivolumab, when combined with other drugs like relatlimab, could be effective for treating melanoma brain metastases.1241014
What safety data exists for Nivolumab + Relatlimab in treating melanoma brain metastases?The provided research does not directly address the safety data for the combination of Nivolumab (Opdivo) and Relatlimab (Opdualag) specifically for melanoma brain metastases. However, it does include studies on the safety of Nivolumab in combination with other drugs like Ipilimumab for melanoma and brain metastases, as well as general safety concerns related to immunotherapy for brain metastases. These studies highlight the importance of monitoring immune-related adverse events and the need for a multidisciplinary approach in managing such treatments.356813
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, you cannot take systemic corticosteroids or other immunosuppressive medications within 14 days of starting the study, except for certain conditions like adrenal replacement. If you're on corticosteroids, a washout period of 10 days is required before starting the trial. It's best to discuss your specific medications with the trial team.
Eligibility Criteria
This trial is for adults with melanoma that has spread to the brain. Participants must have a measurable brain tumor, be able to follow the study plan, and not have had certain previous treatments like checkpoint inhibitors in the metastatic setting or whole-brain radiation. They should not need steroids, be pregnant or breastfeeding, and must use birth control if applicable.Inclusion Criteria
I am 18 years old or older.
I can provide tumor samples in blocks or slides for PD-L1 testing.
I have melanoma with measurable brain metastases.
My tumor is between 0.5cm and 3cm in size, confirmed by MRI.
I don't have brain-related symptoms from cancer and haven't taken steroids in the last 5 days.
I have a brain lesion that has not been treated with targeted radiation.
I am fully active and can carry on all my pre-disease activities without restriction.
Exclusion Criteria
I have a wound, ulcer, or bone fracture that hasn’t healed.
I had cancer before, but it's been treated and I've been cancer-free for over 2 years.
I am on low-dose steroids or other immune-suppressing drugs, but not for an active autoimmune disease.
I have had targeted radiation for more than 5 brain lesions but no whole brain radiation.
I am not pregnant or breastfeeding.
I have a history of cancer spreading to the lining of my brain and spinal cord.
I had precise radiotherapy, not including my brain lesion, within the last week.
I haven't had major surgery or significant injury in the last 14 days, and I don't expect to need major surgery during the study.
I have or had lung inflammation treated with steroids.
Treatment Details
The trial tests combining Nivolumab with Relatlimab against active melanoma brain metastases. It aims to see if this drug combination can control cancer growth in the brain and will also monitor safety and side effects of these drugs when used together.
1Treatment groups
Experimental Treatment
Group I: Relatlimab+NivolumabExperimental Treatment3 Interventions
Participants will receive nivolumab in combination with relatlimab by vein over about 30 minutes on Day 1 of each 28-day study cycle. You may receive up to 25 doses of the study drugs.
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
Find a clinic near you
Research locations nearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Immune checkpoint blockade in patients with melanoma metastatic to the brain. [2021]Metastatic disease to the brain is a frequent manifestation of melanoma and is associated with a very poor outcome. Systemic therapy with cytotoxic chemotherapy provide only a minimal benefit, while surgery and radiotherapy provide in some patients local control but they less frequently affect the overall outcome of melanoma brain metastases (MBM). The advent of active systemic drugs has revolutioned the care of metastatic melanoma, but this benefit has not been translated into intracranial activity. However, since 2010 the anti-CTLA-4 antibody ipilimumab and the BRAF inhibitors, dabrafenib and vemurafenib, have demonstrated initial signs of efficacy in active brain metastases. This chapter reviews the available data and rationale for ongoing and future trials of immune checkpoint-based combination therapy.
Rapid remission of symptomatic brain metastases in melanoma by programmed-death-receptor-1 inhibition. [2018]Although ∼40% of patients with metastatic melanoma develop brain metastases, the presence of brain metastases often precludes enrolment in clinical trials for advanced melanoma. However, the development of symptomatic brain metastases markedly increases mortality. The antiprogrammed-death-receptor-1 antibody pembrolizumab achieves extracranial metastases disease response rates of up to 50%. Here, we report the rapid and sustained response of symptomatic multifocal brain metastases in a melanoma ipilimumab-pretreated patient under pembrolizumab, combined with high-dose dexamethasone therapy during the induction phase of therapy. Complete remission has been maintained for over 1 year of follow-up and has correlated with the response rate observed in the extracranial metastases. Radiological disease response was identified during the first follow-up visit in the absence of adjuvant radiotherapy. This report highlights the need for further clinical studies to specifically address the therapeutic potential of antiprogrammed-death-receptor-1 monotherapy in the management of untreated brain metastases in melanoma.
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]Immunotherapy targeting the PD-1 axis has activity in several tumour types. We aimed to establish the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC).
Improved Risk-Adjusted Survival for Melanoma Brain Metastases in the Era of Checkpoint Blockade Immunotherapies: Results from a National Cohort. [2022]The successes of checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy trials have generated substantial promise for revolutionizing the management of patients with advanced melanoma. However, because early clinical trials of CBIs and BRAFV600-targeted therapy either excluded or included disproportionately fewer cases of melanoma brain metastases (MBMs), the survival benefit of these novel therapies for MBM remains unknown. We, therefore, evaluated the characteristics, management, and overall survival (OS) of patients who presented with cutaneous MBMs during 2010 to 2015 using the National Cancer Database, which comprises 70% of all newly diagnosed U.S. cancers. OS was analyzed with risk-adjusted proportional hazards and compared by Kaplan-Meier techniques. We found that 2,753 (36%) of patients presenting with stage 4 melanoma had MBMs. Following the 2011 FDA approvals for CBI and BRAFV600-targeted therapy, MBM patients demonstrated a 91% relative increase in 4-year OS to 14.1% from 7.4% preapproval (P < 0.001). Postapproval, the proportion of MBM patients who received CBI rose from 10.5% in 2011 to 34.0% in 2015 (P < 0.001). Initial CBI in MBM patients displayed an improved median and 4-year OS of 12.4 months (compared with 5.2 months; P < 0.001) and 28.1% (compared with 11.1%), respectively. These benefits were pronounced in MBM patients without extracranial metastases, in which CBI demonstrated improved median and 4-year OS of 56.4 months (compared with 7.7 months; P < 0.001) and 51.5% (compared with 16.9%), respectively. Using a large national cohort composed of a "real-life" MBM treatment population, we demonstrated the dramatic OS improvements associated with novel checkpoint blockade immunotherapies. Cancer Immunol Res; 6(9); 1039-45. ©2018 AACR.
Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. [2022]Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases.
Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer. [2019]Brain metastases are common among patients with non-squamous non-small-cell lung cancer (NSCLC) and result in a poor prognosis. Consequently, such patients are often excluded from clinical trials. In Italy an expanded access program (EAP) was used to evaluate nivolumab efficacy and safety in this subpopulation outside a clinical trial.
Intracranial antitumor responses of nivolumab and ipilimumab: a pharmacodynamic and pharmacokinetic perspective, a scoping systematic review. [2020]Recently, two phase II trials showed intracranial activity of the immune checkpoint inhibitors nivolumab and ipilimumab in patients with melanoma brain metastases. However, it is generally assumed that large molecules like monoclonal antibodies nivolumab and ipilimumab cannot penetrate and pass an intact blood brain barrier (BBB). In this systematic review we provide a pharmacodynamic and pharmacokinetic consideration of the clinical activity of the immune checkpoint inhibitors nivolumab and ipilimumab in melanoma brain metastases.
Complications associated with immunotherapy for brain metastases. [2023]Median survival after the diagnosis of brain metastases has historically been on the order of months. With the recent development of immune checkpoint inhibitors, intracranial activity and durable responses have been observed in brain metastases on multiple phase 2 clinical trials, which have primarily been conducted in patients with melanoma. Immune-related adverse events related to checkpoint inhibitor therapy of brain metastasis can present unique challenges for the clinician and underscore the need for a multidisciplinary team in the care of these patients. The goal of this review is to address the current knowledge, limitations of understanding, and future directions in research regarding immune therapy trials and neurologic toxicities based on retrospective, prospective, and case studies.
Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients. [2021]Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination with local therapies regardless of treatment line in patients with asymptomatic and symptomatic MBM.
Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). [2021]In patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present the first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients.
Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. [2022]Combination nivolumab plus ipilimumab was efficacious in patients with asymptomatic melanoma brain metastases (MBM) in CheckMate 204, but showed low efficacy in patients with symptomatic MBM. Here, we provide final 3-year follow-up data from the trial.
Nivolumab Plus Relatlimab: First Approval. [2022]Nivolumab plus relatlimab (nivolumab and relatlimab-rmbw; Opdualag™) is a fixed-dose, combination immunotherapy treatment being developed by Bristol Myers Squibb for the treatment of multiple types of advanced cancers. Both drugs are immunoglobulin G4 (IgG4) monoclonal antibodies developed to target immune checkpoints, with nivolumab targeting the programmed cell death protein 1 (PD-1) receptor and relatlimab being a newly developed, first-in-class drug targeting the lymphocyte-activation gene 3 (LAG-3) protein. In March 2022, nivolumab plus relatlimab received its first approval in the USA for the treatment of unresectable or metastatic melanoma in adult patients and paediatric patients aged ≥ 12 years who weigh ≥ 40 kg. This article summarizes the milestones in the development of this combination therapy leading to this first approval for unresectable or metastatic melanoma.
Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]We characterized the safety of first-line nivolumab plus ipilimumab (NIVO+IPI) in a large patient population with metastatic NSCLC and efficacy outcomes after NIVO+IPI discontinuation owing to treatment-related adverse events (TRAEs).
The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab. [2023]The combination of nivolumab + relatlimab is superior to nivolumab alone in the treatment of naive patients and has activity in PD-1 refractory melanoma. We had previously observed a reduced expression of LAG3 in melanoma tissue from patients with type 2 diabetes.