With SX-682 currently in clinical trials for the treatment of metastatic melanoma in combination with anti-PD1 in instances where there is resistance to ICI therapy, we propose that an alternative option may be to treat ICI-resistant BRAF wild-type melanoma with the combination of CDK4/6, CDK2, and CXCR2 antagonists. This evidence concerns the gene CDK4 and metastatic melanoma.