Online Program

Return to main conference page
Tuesday, September 24
Tue, Sep 24, 11:45 AM - 1:00 PM
Various Rooms
Roundtable Discussions

TL11: Practical Considerations of Emerging Innovative Dose-Escalation Methods in Oncology (300838)

*Wei Zhang, Eli Lilly and Company 

Keywords: dose-finding designs, early-phase clinical trials, oncology

Room: Marriott Balcony A

Dose-escalation is a critical component in drug development. The main purpose of dose-escalation in oncology clinical trials is to identify the maximum tolerated dose (MTD), which is then tested further to establish a recommended phase 2 dose (RP2D). In recent years, some innovative dose-escalation methods have emerged and gradually gained popularity. Some of these methods are based on an existing and well-established framework, such as Continual Reassessment Method (CRM) or Toxicity Probability Interval (TPI), but with improved properties (e.g., excessive toxicity control) or to tackle new problems (e.g., delayed toxicity). Others are traditional methods, e.g. accelerated titration design with or without intra-patient dose escalation, that have also been applied implicitly to meet specific drug development needs. Depending on the mechanism of action of a specific regimen, the expected toxicity profile, and the overall drug development strategic plan, there are practical considerations on selecting the most appropriate dose-escalation method to achieve optimal accuracy, safety, speed, and sample size. For example, dose-limiting toxicities are usually rare for immune-oncology compounds and some target therapies, and the MTD may never be reached. We will discuss these practical considerations at this roundtable.