ABSTRACT

Currently only 5% of investigational new drug (IND) applications to the Food and Drug Administration (FDA) in oncology result in clinically approved agents [1,2]. This is a very serious problem, since the development of a new agent is a lengthy and expensive process and many of these agents fail relatively late in that process. The fact that an increasing proportion of IND anticancer agents are molecularly targeted suggests testing the agent for effectiveness against the target by means of a PD assay very early in the drug development process. This is particularly useful and important since the pre-clinical tests of such effectiveness are often misleading, yielding both false-positive and false-negative results. For this reason, the FDA issued a new Exploratory IND (expIND) Guidance in 2006, to allow for such studies as small first-in-man trials, conducted at dose levels and administration schedules not expected to result in significant clinical toxicity, and generally restricted to at most approximately 1 week per patient [1,2]. Conducting studies under this guidance 74requires substantially less pre-clinical toxicology work than is required for standard IND phase 1 studies [1,2]. Therefore, phase 0 studies can be administered while the toxicology studies preparatory to filing a standard IND are being conducted, and they will not postpone the time until the phase 1 trial can be initiated.