An improved understanding of the biology of cancer has led to remarkable progress in therapeutic approaches. Anticancer agents developed over the last 2 decades utilize multiple mechanisms of action including conventional cytotoxic agents as well as inhibition of oncogenic signalling pathways and angiogenesis. More recently, ‘immunotherapy’ agents that rely on immunomodulatory mechanisms to target and destroy cancer cells, most notably immune checkpoint inhibitors (ICPis), have been developed.

The first ICPi approved by the United States Food and Drug Administration (FDA) was ipilimumab, a fully humanized immunoglobulin G1 monoclonal antibody that blocks cytotoxic T-lymphocyte antigen. Pembrolizumab and nivolumab were the first ICPis that target programmed cell death protein 1; they showed high response rates with favourable toxicity profiles and were approved for treating metastatic melanoma in 2014. The notable successes of these pivotal trials may have led to unrealistically high expectations among patients and clinicians, as more recent studies have shown that only a subset of patients exhibit durable responses, and existing checkpoint-blocking monotherapies seldom lead to complete remission. These findings have prompted the search for next-generation ICPis as well as evaluations of their combinations with other biologic agents.