Ongoing clinical trials and novel development approaches focus on poor prognosis groups (e.g., anti-PD-1 refractory melanoma, brain metastases, and uveal melanoma) in order to further ameliorate outcomes of systemic therapy and to further improve long-term survival for patients with metastatic melanoma, even for those with a dismal prognosis today. This evidence concerns the gene PDCD1 and metastatic melanoma.