Master protocols in immuno-oncology: do novel drugs deserve novel designs?

The rapid rise to fame of immuno-oncology (IO) drugs has generated unprecedented interest in the industry, patients and doctors, and has had a major impact in the treatment of most cancers. An interesting aspect in the clinical development of many IO agents is the increasing reliance on nonconventional trial design, including the so-called 'master protocols' that incorporate various adaptive features and often heavily rely on biomarkers to select patient populations most likely to benefit. These novel designs promise to maximize the clinical benefit that can be reaped from clinical research, but are not without costs. Their acceptance as solid evidence basis for use outside of the research context requires profound cultural changes by multiple stakeholders, including regulatory bodies, decision-makers, statisticians, researchers, doctors and, most importantly, patients. Here we review characteristics of recent and ongoing trials testing IO drugs with unconventional design, and we highlight trends and critical aspects.
Competing Interests: Competing interests: GC received honoraria for speaker, consultancy or advisory role from Roche, Pfizer, Novartis, Seattle Genetics, Lilly, Ellipses Pharma, Foundation Medicine, and Samsung.
(© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)