Immunotherapy of cancer has had a long history of development, starting from pioneering efforts in using coley toxins to treat patients—a therapeutic approach named after Dr. William Coley. Even though these earlier efforts never turned into a standard treatment, further investigations on the relationships between tumor cells and the immune system led to discoveries which unveiled fundamental principles underlying cancer progression, such as immune surveillance, cancer dormancy, cancer immuno-editing, and the cancer immunity cycle.

These discoveries were foundational for clinical successes and corresponding regulatory approvals in recent years, of therapies targeting the CTLA-4, PD-1, and PD-L1 immune checkpoints. In the wake of these successes, there has been an explosion in the development of immuno-modulating, anti-cancer pharmacological modalities, leading to the initiation of, literally, thousands of clinical trials. However, from the discovery phase to late-stage clinical testing and regulatory approval, challenges in the development of immuno-oncology (IO) drugs are multi-fold and complex, with related complexities in the design of clinical trials; if unaddressed, these may lead to a decreased probability of success...