Despite advances in technology and our understanding of the genetic and molecular underpinnings of cancer, making a meaningful impact on the survival and quality of life of patients with cancer remains a significant challenge. In fact, a recent review revealed that, among 59 cancer drugs approved by the U.S. Food and Drug Administration (FDA) based on the surrogate endpoint of response rate, only six showed overall survival benefit. A separate review of 93 cancer drug indications that were granted accelerated approval by the FDA showed that only 20 percent demonstrated improvement in overall survival in confirmatory trials, and that 20 percent showed improvement on the same surrogate measure used in both preapproval and confirmatory trials.
These findings underscore the importance of well-designed early phase oncology trials for establishing meaningful safety and efficacy signals for investigative cancer drugs. Historically, Phase 1 oncology trials have been thought of as studies for establishing the toxicity profile of novel therapeutic agents, with low clinical utility in terms of establishing efficacy. However, the traditional clinical trial paradigm involving three distinct trial phases has shifted with the advent of targeted therapies and immunotherapies, and we are seeing an increasing number of Phase 1 trials reporting preliminary response rates.
In this article, we discuss critical design considerations for early phase oncology studies and explore the use of adaptive designs for optimizing these studies to support later stage success.