Subcutaneous Nivolumab + Relatlimab for Melanoma
(RELATIVITY-127 Trial)
Recruiting in Palo Alto (17 mi)
+319 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Bristol-Myers Squibb
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This trial is testing two ways of giving a combination of two drugs, nivolumab and relatlimab, to patients with advanced melanoma that hasn't been treated before. One method involves injecting the drugs under the skin, while the other involves injecting them into a vein. These drugs help the immune system recognize and attack cancer cells.
Will I have to stop taking my current medications?
The trial requires that participants do not take systemic corticosteroids or other immunosuppressive medications within 14 days before starting the study treatment. Inhaled or topical steroids are allowed if you don't have an active autoimmune disease.
What data supports the effectiveness of the drug Nivolumab + Relatlimab for melanoma?
In the RELATIVITY-047 trial, the combination of nivolumab and relatlimab significantly improved the time patients lived without their melanoma getting worse compared to nivolumab alone, while maintaining stable quality of life.
12345Is the combination of Nivolumab and Relatlimab safe for treating melanoma?
The combination of Nivolumab and Relatlimab, known as Opdualag, has been approved for treating advanced melanoma. While it improves survival, it is associated with more frequent serious side effects compared to Nivolumab alone.
35678What makes the drug Nivolumab + Relatlimab unique for treating melanoma?
Nivolumab + Relatlimab is unique because it combines two immunotherapy drugs that target different immune checkpoints, PD-1 and LAG-3, to enhance the body's immune response against melanoma. This fixed-dose combination has shown improved progression-free survival in patients with unresectable or metastatic melanoma compared to nivolumab alone.
12369Eligibility Criteria
This trial is for people aged 12 and older with Stage III (unresectable) or Stage IV (metastatic) melanoma, as per AJCC staging. They must have measurable disease by CT or MRI, be in good physical condition (ECOG ≤1), and adolescents must weigh at least 40 kg. It's not for those with ocular melanoma, a history of myocarditis, or on high-dose steroids/immunosuppressants.Inclusion Criteria
My melanoma is at Stage III (unresectable) or IV (metastatic).
I am very active or have minor symptoms that don't limit my daily activities.
My melanoma is at Stage III (unresectable) or Stage IV (metastatic).
+2 more
Exclusion Criteria
I do not have eye melanoma.
I haven't taken high-dose steroids or immunosuppressants in the last 14 days.
I have never had myocarditis.
Participant Groups
The study tests if the subcutaneous form of Nivolumab + Relatlimab combination is as effective as the intravenous version in untreated metastatic/unresectable melanoma patients. The focus is on comparing drug exposure levels between these two methods.
2Treatment groups
Experimental Treatment
Active Control
Group I: Nivolumab + Relatlimab FDC SCExperimental Treatment2 Interventions
Group II: Nivolumab + Relatlimab FDC IVActive Control1 Intervention
Nivolumab + Relatlimab Fixed-dose Combination (FDC) is already approved in United States for the following indications:
🇺🇸 Approved in United States as Opdualag for:
- Advanced melanoma (unresectable or metastatic)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Highlands Oncology Group (HOG) - Fayetteville - North Hills LocationSpringdale, AR
Tom Baker Cancer Centre (TBCC) - Alberta Health Services (AHS)Calgary, Canada
Sunnybrook Health Sciences CentreToronto, Canada
Ottawa Hospital Research InstituteOttawa, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Bristol-Myers SquibbLead Sponsor
References
Successful Treatment of Multiple Metastatic Melanoma with Nivolumab, Ipilimumab plus Denosumab Combined Therapy. [2020]Nivolumab plus ipilimumab combined therapy is one of the promising drugs that enhance the anti- immune response in patients with advanced melanoma. Therefore, to increase its response rate is of great interest to dermatologists. Recent reports suggested that, since CD8+ T cells after the administration of ICIs increase the RANKL expression to induce an immunosuppressive tumor microenvironment in melanoma, denosumab might enhance the anti-tumor effects of immune checkpoint inhibitors, such as nivolumab and ipilimumab. In this report, we present a case of multiple metastatic melanoma with nivolumab, ipilimumab plus denosumab combined therapy.
Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod. [2020]Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.
Health-related quality of life with nivolumab plus relatlimab versus nivolumab monotherapy in patients with previously untreated unresectable or metastatic melanoma: RELATIVITY-047 trial. [2023]In the phase II/III RELATIVITY-047 trial, a novel fixed-dose combination (FDC) of nivolumab plus relatlimab (NIVO + RELA; a programmed death-1 and a lymphocyte-activation gene 3 inhibitor, respectively) significantly improved progression-free survival (PFS) versus NIVO in patients with previously untreated unresectable or metastatic melanoma (median follow-up, 13.2 months) with stable health-related quality of life (HRQoL), although grade three or four treatment-related adverse events (TRAEs) were more frequent with the combination. Updated HRQoL results (median follow-up, 19.3 months) are presented.
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]Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma.
Nivolumab + ipilimumab ups melanoma response. [2018]For patients with advanced melanoma, the combination of ipilimumab and nivolumab yields better responses than ipilimumab alone. However, the two-drug combination is much more likely to cause side effects than the monotherapy.
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.
Nivolumab monotherapy or in combination with ipilimumab for metastatic melanoma: systematic review and meta-analysis of randomized-controlled trials. [2023]Nivolumab, a completely human programmed death-1 inhibitor antibody, was first approved by the Food and Drug Administration for patients with advanced malignant melanoma resistant to other modalities of treatment. In 2015, it received approval as the first line of treatment for malignant melanoma. We aimed to synthesize evidence from published randomized-controlled trials on the safety and efficacy of nivolumab, either alone or in combination with ipilimumab, in the management of advanced unresectable melanoma. We searched the following electronic databases: PubMed, Scopus, Web of Science, and Cochrane Central. The records retrieved were screened for eligibility. Time-to-event data were pooled as Hazard ratio using the generic inverse variance method and dichotomous data were pooled as relative risk (RR) in a random-effects model. We used Review Manager 5.3 software for windows. Four unique randomized-controlled trials (five reports) with a total of 1910 patients (nivolumab group, n=1207 and control group, n=703) were included. The overall effect estimate favored nivolumab plus ipilimumab versus ipilimumab alone in terms of the objective response rate [RR: 3.58, 95% confidence interval (CI): 2.08-6.14], the complete response rate (RR: 5.93, 95% CI: 2.45-14.37), the partial response rate (RR: 2.80, 95% CI: 2.16-3.64), the stable disease rate (RR: 0.56, 95% CI: 0.41-0.76), and progression-free survival (hazard ratio: 0.67, 95% CI: 0.60-0.74). The pooled studies were homogenous. Similar results were obtained for nivolumab monotherapy versus chemotherapy comparison. Nivolumab alone or combined with ipilimumab significantly improved the overall and complete response rates compared with ipilimumab alone. In addition, nivolumab resulted in longer progression-free survival with a comparable safety profile.
Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]Recent studies suggest that combining nivolumab with ipilimumab is a more effective treatment for melanoma patients, compared to using ipilimumab or nivolumab alone. However, treatment with these immunotherapeutic agents is frequently associated with increased risk of toxicity, and (auto-) immune-related adverse events. The precise pathophysiologic mechanisms of these events are not yet clear, and evidence from clinical trials and translational studies remains limited. Our retrospective analysis of ~7700 metastatic melanoma patients treated with ipilimumab and/or nivolumab from the FDA Adverse Event Reporting System (FAERS) demonstrates that the identified immune-related reactions are specific to ipilimumab and/or nivolumab, and that when the two agents are administered together, their safety profile combines reactions from each drug alone. While more prospective studies are needed to characterize the safety of ipilimumab and nivolumab, the present work constitutes perhaps the first effort to examine the safety of these drugs and their combination based on computational evidence from real world post marketing data.
[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]The case was analyzed for response to nivolumab (Opdivo) monotherapy in a patient with recurrent skin melanoma (10x6x6 cm) and disease dissemination (with multiple lung metastasis), positive for BRAF mutation that followed upon the local therapy (surgical excision) and 6 cycles of adjuvant chemotherapy (at CVD regimen - cisplatin, vinblastine, dacarbazine). Histological results: melanoma. Immunohystochemical: S 100-positive; Melan A - positive; HMB45 - positive, AE1/AE3 - negative, p53 - positive in most cells, vim - positive, ɑ sma - weak in most cells, Ki67 - positive in 20%, BRAFmut, ECOG performance status 1, LDH - 1320 U/L (N