Statistical Designs and Considerations for Dose Optimization with Drug Combination and Multiple Indication

External Institution: The University of Texas MD Anderson Cancer Center

External Collaborators: Ying Yuan, PhD (Co-PI); Ruitao Lin, PhD (Co-PI); Suyu Liu, PhD (Co-PI); Timothy A. Yap, MD, PhD

FDA Collaborators: Anup Amatya, PhD; Jonathon Vallejo, PhD; Mirat Shah, MD, MHS; Atiqur Rahman, PhD; Jingyan Wang, PhD; Ting-Yu Chen, PhD; Yiming Zhang, PhD

Date Started: 9/30/2025

Regulatory Science Challenge  

A major challenge in cancer drug development is improving how dosages which maximize benefit/risk are identified and investigated. Traditional methods focus on finding the maximum tolerated dose (MTD), but this is often irrelevant for new therapies, which can potentially be just as effective at lower doses with fewer side effects. To address this, FDA Oncology Center of Excellence launched Project Optimus to support selecting an optimized dosage that balances efficacy, safety, and tolerability of the treatment. Although some guidelines have been developed to identify the optimized dosage for single drugs with one disease indication, it is still unknown how to best determine the optimized dosages through randomized dose-selection trials, as well as for combination therapies and across multiple indications.

Project Goals and Objectives

The overall objective of this project is to develop better statistical methods to improve how optimized dosages are chosen for cancer drugs. The aims are to develop statistical methods that 1) incorporate information on patient tolerability and drug exposure, 2) evaluate how each drug in a combination treatment contributes to the optimized dosage, 3) identify optimized dosages specific to the patient's cancer type, and to (4) develop user-friendly software implementing the methodology. This project aims to enhance drug development efficiency and safety, and to help patients receive the drug dosage with the best benefit-risk profile.