ABSTRACT
From the identification of oncogenes that drive tumor proliferation and new classes of agents to inhibit oncogenic pathways and/or specific mutated oncogenes, the field of molecularly targeted therapy was born. The initial trials were straightforward, one drug-one disease-one mutation, but soon it became clear that a tenant of molecular targeted therapy is that the driving aberration may be more important than the underlying disease. More recently, the concept of developing targeted agents against specific targets that present across multiple malignanant diseases have led to the development of so-called “basket” trials, as well as the development of studies testing multiple drugs against multiple molecular targets in an individual disease, the so-called umbrella trials. In this chapter, the evolution of the targeted therapy clinical trial landscape is described with a focus on how a number of challenges have been overcome, culminating in numerous multi-arm, multi-drug targeted therapy trials opening in recent years.
