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While the incidence of melanoma continues to rise, the mortality of the disease appears to have stabilized. This may, in part, be due to the development and application of immune checkpoint inhibitors as standard of care in advanced melanoma. However, many patients do not respond to these therapies alone. Combining immune checkpoint inhibitors with other classes of therapeutics appears to be a promising direction to improve response and survival in advanced melanoma. This review article aims to discuss phase 1 and 2 clinical trials examining immune checkpoint inhibitors in combination therapy for the treatment of advanced, unresectable melanoma. In particular, these regimens include various kinase inhibitors, tumor-infiltrating lymphocytes, toll-like receptor agonists, cytokines, and oncolytic viral therapies. The combinations under discussion include both systemic and combination systemic/local therapies. Drug combinations discussed here appear to be promising therapeutic regimens for advanced melanoma. Improved understanding of the mechanisms of primary, adaptive, and acquired resistance to immune checkpoint inhibitors may guide the development of future combination regimens.

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The treatment of advanced melanoma: a review of systemic and local therapies in combination with immune checkpoint inhibitors in phase 1 and 2 clinical trials