Immuno-Oncology: Managing Tomorrow's Responses Today — Delayed Outcomes In Dose Escalation Trials

By Matthew Confeld, PharmD PhD, Associate Director, Clinical Research Methodology; Amit Sharma, MD, Medical Director, Medical Affairs, Oncology and Rare Disease; and Michael F Murphy, MD PhD, Chief Medical and Scientific Officer

The advent of immunotherapy has revolutionized cancer treatment, starting with bladder cancer in 1990 through the use of Bacillus Calmette-Guérin (BCG), a weakened live bacterium. While 70% of bladder cancer patients achieved remission with BCG therapy, it wasn't until 2011 that immunotherapy significantly expanded with the approval of the targeted checkpoint inhibitor Yervoy® (ipilimumab). This breakthrough was followed by the introduction of PD-1/PD-L1 inhibitors, such as pembrolizumab, further transforming cancer treatment strategies.

Despite these advancements, the immune system's complex mechanisms remain only partially understood, leading to a range of side effects that can emerge weeks to months after the initiation of treatment. These side effects, which affect various organ systems, have prompted recent guidelines from organizations like the American Society of Clinical Oncology and the Society for Immunotherapy of Cancer. These guidelines provide frameworks for managing immune-related adverse events (irAEs) that may appear long after therapy begins.

To address these challenges effectively, innovative clinical trial designs are crucial. Such designs should be tailored to capture and assess delayed toxicities and efficacy responses in early-phase research. This approach will help in the optimal development of new immunological targets and combination therapies, ensuring that advancements in immunotherapy continue to benefit patients while managing potential risks.