CTLA4 and melanoma: For these patients, combination of anti-CTLA-4 and anti-PD-1 therapies have been shown to have complementary activity of up to 50-60% response rates in advanced Stage III or IV melanoma, but, disappointingly, they act synergistically to amplify immune-related adverse events (irAEs) and severe toxicity in up to 60% of all patients 3, 5.