The purpose of this research study is to compare any good and bad effects of giving ipilimumab, nivolumab, and GM-CSF (Sargramostim) at the same time compared to just ipilimumab and nivolumab together for advanced melanoma. It would also like to find out what effects, good and bad, this combination of drugs may have on the cancer. 

This study will involve the addition of the U.S. Food and Drug Administration (FDA)-approved agent nivolumab to the standard FDA-approved ipilimumab immunotherapy in the hopes that it might further improve the good effects of the immunotherapy component of the treatment sequence. The combination of ipilimumab and nivolumab has been shown in recent studies to produce superior antitumor effects but also more side effects than ipilimumab alone. This combination has received FDA approval for patients with BRAF V600 wild-type unresectable or metastatic melanoma. This combination is under review for FDA approval for patients with BRAF V600 mutant melanoma and is therefore still considered to be experimental for these patients. 

GM-CSF is a protein that your body normally produces to signal to your body to make white blood cells. White blood cells are very important in the body’s defense system as they help identify and destroy foreign invaders, such as bacteria, viruses, and cells that don’t belong, such as cancer cells. Injections of GM-CSF increase your body’s production of white blood cells and also help enhance the function of the white blood cells. This research study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To be better, the study drugs should improve how long participants are able to live with their cancer compared to the usual approach. 

This research study has two study groups, Arm A and Arm B. A computer will by chance assign participants to treatment groups. Arm A will receive the study drugs nivolumab, ipilimumab, and GM-CSF, followed by just nivolumab and GM-CSF. Arm B will receive nivolumab, and ipilimumab, followed by just nivolumab.

Total study participation will last approximately 5 years.