Keywords: oncology, adaptive design, multi arm designs
The advancements in oncology research over the last few decades has led to the identification of molecular mechanisms underlying the key oncogenic factors and a generation of targeted therapies and their combinations. Historically such combination therapies have been developed as add-on therapies combining a new molecular entity(NME) with an existing Standard of care (SoC). However given the increasing numbers of NME’s under development its natural to consider rational combinations of two or more novel NMEs. Such combinations require re-examination of our existing clinical trial designs and suggests that a new developmental model may facilitate co-development of multiple NMEs in combination in a more efficient manner.
There is existing regulatory guidance from the FDA and CHMP that provides a mechanism for approval for such combination NMEs typically by the demonstration of the contribution of each agent to the claimed effects of the combination in comparison to the standard of care unless otherwise demonstrated during earlier stages of development. In most cases depending on the level of evidence, the confirmatory study may be required to be a full factorial design or a smaller subset of it including the arms for combinations and its components to answer these questions.
The objective of this roundtable discussion is to share examples of such multi-combination development of NMEs within the existing regulatory framework and discuss the statistical topics that are pertinent to such co-development strategies.