DROID: dose-ranging approach to optimizing dose in oncology drug development

Area of Science:

• Oncology
• Pharmacology
• Clinical Trial Design

Background:

• Traditional chemotherapy dose-finding paradigms are increasingly questioned for targeted oncology drugs.
• The US Food and Drug Administration (FDA) launched Project Optimus to reform oncology drug dose optimization.
• There is a need for efficient dose optimization strategies for targeted cancer therapies.

Purpose of the Study:

• To propose and evaluate a novel dose-ranging approach to optimizing dose (DROID) for targeted oncology drug development.
• To align oncology drug development with the FDA's Project Optimus and guidance on dose optimization.
• To establish a new paradigm for optimizing doses in oncology trials.

Main Methods:

• DROID is a two-stage approach leveraging established dose-ranging study frameworks.
• Stage 1: Adaptive dose assignment to establish therapeutic dose range (TDR) and recommended phase 2 dose set (RP2S).
• Stage 2: Randomized assessment of dose-response within RP2S to identify the optimal dose.

Main Results:

• Simulations demonstrate DROID significantly outperforms conventional dose optimization methods.
• DROID efficiently identifies optimal doses for targeted oncology drugs.
• The approach aligns with FDA recommendations for randomized, parallel dose-response trials.

Conclusions:

• DROID provides an efficient and effective paradigm for optimizing targeted oncology drug doses.
• This approach addresses the limitations of "more is better" in oncology drug development.
• DROID facilitates alignment with current regulatory initiatives for dose optimization.