Plain language summary of the RELATIVITY-098 study results: nivolumab plus relatlimab given after melanoma is removed by surgery

Plain Language SummaryWhat is this summary about?In this article, we summarize the main goals and findings of the RELATIVITY-098 clinical trial, which tested whether adding relatlimab to nivolumab compared with nivolumab alone reduces the chance of cancer coming back after surgery in people with stage III or IV melanoma (skin cancer) that had been completely removed by surgery.Nivolumab alone is a treatment that activates a person’s immune system and is approved to treat patients with melanoma that has been removed by surgery as well as for patients with melanoma that cannot be removed by surgery. Nivolumab plus relatlimab is a therapy combination that activates a person’s immune system in 2 different ways and has been shown to be more effective compared with nivolumab alone for patients with melanoma that cannot be removed by surgery.This study tested whether nivolumab plus relatlimab is more effective than nivolumab alone for patients with melanoma that has been removed by surgery.How was the study designed?This was a phase 3 study. In phase 3 studies, a large number of people are recruited to determine whether a new treatment is safe and effective. It is the final stage before the treatment is submitted for approval by health authorities. During this study, 1093 people with stage III or IV melanoma that had been completely removed by surgery were randomly assigned to receive either nivolumab plus relatlimab or nivolumab alone. Patients and doctors did not know which treatment each person received during the study. The researchers assessed whether the combination reduced the chance of cancer coming back (recurrence-free survival [RFS]) compared with nivolumab alone.What are the key takeaways?The study did not meet its main goal. Researchers found that people who took nivolumab plus relatlimab were as likely to have cancer come back as people who took nivolumab alone (i.e.; RFS was similar between groups). Since there was no meaningful improvement in RFS with the combination compared with nivolumab alone, the study sponsor announced the study did not achieve its objectives.Since the combination treatment did not show an improvement in preventing melanoma from returning, the researchers did not complete the planned analysis of overall survival (how long people lived after treatment). Safety findings were consistent with what is already known about these drugs, and no new safety concerns were identified. Additional analyses were performed to help scientific understanding of the study outcome but did not change the primary result that the combination of the drugs did not reduce the risk of melanoma coming back compared with nivolumab alone.What were the main conclusions reported by the researchers?This study found that adding relatlimab to nivolumab after complete surgical removal of stage III or IV melanoma did not lower the chance of melanoma coming back compared with nivolumab alone. Overall, these results mean that nivolumab plus relatlimab is not more effective than nivolumab alone as adjuvant (post-surgery) treatment for patients with stage III or IV melanoma that has been removed by surgery.Clinical trial number: NCT05002569