Translating RELATIVITY-020 Part E Dosing Insights to Clinical Practice

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EP: 1.Translating RELATIVITY-020 Part E Dosing Insights to Clinical Practice

EP: 2.Case Study: Sarah’s Journey with High-Burden BRAF V600E Melanoma

The discussion opened by reviewing the evolving treatment landscape for metastatic melanoma, particularly in patients with BRAF-mutant disease and high tumor burden. In a typical case, like a 46-year-old patient with multiple pulmonary and hepatic lesions, selecting between immune checkpoint combinations and targeted therapies depends on disease symptoms, patient preferences, and therapeutic goals. While immunotherapy combinations like nivolumab with ipilimumab or relatlimab are favored for durable responses, targeted therapy may offer faster symptom relief. Given this patient’s motivation, intact performance status, and normal LDH, immune-based therapy would be a strong frontline option.

The group also reviewed new data from the RELATIVITY-020 study, which examined different dosing strategies for the LAG-3 inhibitor relatlimab. The randomized trial compared standard-dose relatlimab (160 mg) with a higher dose (480 mg) in combination with nivolumab. Despite a slight increase in response rate with the higher dose, it also led to more toxicity. Progression-free and overall survival were similar between arms, supporting continued use of the standard-dose regimen due to its better balance of efficacy and tolerability. This reinforces the clinical value of maintaining a favorable safety profile, especially when long-term treatment is anticipated.

Looking ahead, ongoing trials of other LAG-3 agents like fianlimab combined with cemiplimab may further shift the treatment paradigm. These drugs, although similar in target, are structurally different and dosed differently—raising open questions about optimal exposure, efficacy, and toxicity. Early data suggest fianlimab may have higher response rates, but its true clinical value will depend on larger phase 3 trials. Until then, clinicians are guided by existing evidence supporting nivolumab-relatlimab as an effective and tolerable option for patients with metastatic melanoma, particularly those with a manageable disease burden and no urgent need for rapid tumor shrinkage.