The Master Protocol Concept

During the past decade, biomedical technologies have undergone an explosive evolution—from the publication of the first complete human genome in 2003, after more than a decade of effort and at a cost of hundreds of millions of dollars—to the present time, where a complete genomic sequence can be available in less than a day and at a small fraction of the cost of the original sequence. The widespread availability of next-generation genomic sequencing has opened the door to the development of precision oncology. The need to test multiple new targeted agents both alone and in combination with other targeted therapies, as well as classic cytotoxic agents, demands the development of novel therapeutic platforms (particularly Master Protocols) capable of efficiently and effectively testing multiple targeted agents or targeted therapeutic strategies in relatively small patient subpopulations. Here, we describe the Master Protocol concept, with a focus on the expected gains and complexities of the use of this design. An overview of Master Protocols currently active or in development is provided along with a more extensive discussion of the Lung Master Protocol (Lung-MAP study).