Described herein are therapeutic methods for subjects having an unresectable locally advanced or metastatic cancer. The method includes administration of engineered anti-IL-2 antibodies in combination with an initial low dose of IL-2 and further include administration of at least one booster low doses of IL-2. Also described herein are combination therapies comprising engineered anti-IL-2 antibodies in combination with an immune checkpoint inhibitor such as nivolumab and an initial low dose of IL-2 and related therapeutic methods for subjects having an unresectable locally advanced or metastatic cancer, for example but not limited to cutaneous melanoma.