Dose Optimization in Drug Development
Chair: Victoria Chang (JBS | BeiGene)
Speaker: Kentaro Takeda, PhD (Astellas)
Title: A Bayesian Optimal Interval Design for Dose Optimization with a Randomization Scheme Based on Pharmacokinetics Outcomes in Oncology
Abstract: The primary objective of an oncology dose-finding trial for novel therapies, such as molecularly targeted agents and immune-oncology therapies, is to identify the optimal dose (OD) that is tolerable and therapeutically beneficial for subjects in subsequent clinical trials. Pharmacokinetic (PK) information is considered an appropriate indicator for evaluating the level of drug intervention in humans from a pharmacological perspective. Several novel anticancer agents have been shown to have significant exposure-efficacy relationships, and some PK information has been considered an important predictor of efficacy. This paper proposes a Bayesian optimal interval design for dose optimization with a randomization scheme based on PK outcomes in oncology. A simulation study shows that the proposed design has advantages compared to the other designs in the percentage of correct OD selection and the average number of patients allocated to OD in various realistic settings.
Speaker: Chester Lin, PhD (BeiGene)
Title: Exposure Informed Dose Selection
Abstract: Dose selection is one of the most difficult and important decisions that need to take place during the clinical trials. In practice, the traditional dose-response model may not perform well when an assigned dose is poorly correlated with plasma concentrations, obscuring an existing concentration-response relationship. It also suffers from the limited number of fixed doses in the dose-response studies. Recently, FDA suggested using measurement of systemic exposure levels as part of dose-response study to provide additional information to overcome these issues. In this presentation, we will introduce a methodology engaging dose selection with exposure response analysis and evaluate it in computer simulations.
Speaker: Lei Gao, PhD (Moderna)
Title: Strategies for Successful Dose Optimization in Oncology Drug Development: A Practical Guide
Abstract: Dose-finding is a formidable challenge in drug development. Historically, dose determination in oncology and non-oncology has followed divergent paths due to the unique characteristics of each therapeutic area. However, with the emergence of new generation treatments in oncology, such as targeted therapies, cytostatic agents, and immune therapies, the dose-response relationship for efficacy and toxicity is demonstrating a different profile compared to the past. The doses below the MTD may demonstrate similar efficacy to the MTD with an improved tolerability profile, resembling what is commonly seen in non-oncology treatments. This talk delves into the historical evolution of dose finding from non-oncology to oncology, highlighting examples and summarizing the underlying drivers of change. Subsequently, a practical framework and guidance are provided to illustrate how dose optimization can be incorporated into various stages of the development program.
