Opportunities and challenges in addressing dose optimization in pivotal trials

Music City Center 

Advancement of oncology and hematology drug development has brought many innovative medicines in recent years, such as immuno-therapies and CAR-T therapies. Because of the enormous unmet medical need and severity of the disease burden, oncology drug development has traditionally focused on identifying the maximum tolerated dose (MTD) in phase I and moving quickly to phase III, sometimes utilizing a single arm trial at the MTD for accelerated approval. Recently, regulatory authorities have been emphasizing evaluation of the benefit risk in dose optimization and moving towards minimum effective dose (MED) before entering phase 3 development. In this presentation, we will discuss the challenges in identifying the optimal dose in pivotal trials. We will discuss the idea of evaluating dose optimization using inferential seamless phase II/III adaptive design to accelerate clinical development. In addition, we will highlight a few key issues surrounding the use of biomarkers and quantitative measures of benefit and risk for selecting the optimal dose, the analysis of clinical outcomes based on combined data from both phases II and III, as well as blinding and trial integrity with interim adaptation.

Dose optimization

Adaptive design

benefit risk