We are doing this study to find the most effective, safe dose of a combination of the drugs fianlimab and ceminplimab. We want to know if this combination is an option for people with melanoma. We will compare how well this drug combination works to the usual treatment of relatlimab and nivolumab, which has the brand name Opdualag®.

Advanced or Metastatic Melanoma

Adults ages 18+ who:

• Are diagnosed with stage III and stage IV (metastatic) melanoma
• Have disease that is unresectable (cannot be removed by surgery)
• Have not received any prior systemic therapy for unresectable or metastatic melanoma

For more information about who can join this study, please contact the study team at WakeCountyOncResearch@dm.duke.edu or 919-954-3085.

If you choose to join this study, you will get a random assignment (like a coin flip) to either:

• Get a dose of fianlimab + cemiplimab every 3 weeks; OR
• Get a dose of Opdualag every 4 weeks

Both the study drug combination and Opdualag are given into a vein using a needle. This is called an intravenous (IV) infusion.

You will take your assigned study regimen for as long as the study doctor believes you are getting a benefit.

The following tests and procedures will be performed throughout the study:

• Physical exams
• Blood draws and urine samples
• Tumor biopsy
• Imaging (MRI/CT)

We will schedule you to come in for some return visits after you stop taking your study regimen. We will keep in touch with you to see how you are doing for up to 6 years after the final participant finishes the study.