Key Considerations When Designing A Phase 1 Oncology Trial

By Luke Gill

Traditionally, phase 1 oncology trials have relied on a standard 3+3 dose escalation design to achieve the objective of defining a recommended phase 2 dose (RP2D). However, statistical simulations have shown that as few as one in three trials using the 3+3 design succeed in identifying the maximum tolerated dose. Concerns have also been raised that this method of dose escalation may result in a high percentage of patients being treated at subtherapeutic doses. With the advent of molecularly targeted agents (MTAs) and immunotherapies, which have toxicity profiles that are distinct from those of cytotoxic agents, we are increasingly seeing innovative phase 1 trials that may be better suited to dose-finding studies of novel therapeutics.