Combination Therapy Dose Optimization In Oncology Trials

By Jeffrey Hodge, MS, Vice President Early Phase Oncology, Hematology-Oncology Center of Excellence, David Alsadius, MD, PhD, Senior Medical Director, Solid Tumor Lead, Hematology-Oncology Center of Excellence, Jennifer Underwood, MSc, Senior Therapeutic Strategy Director, Oncology, Zheng Liu, DSc, Director, Quantitative Clinical Pharmacology, and Bryce Davies, MSc, Head of APAC Strategy, Early Phase Oncology and Innovative Therapies

The shift in oncology research is moving away from the "more is better" philosophy of the Maximum Tolerated Dose. As the field pivots toward sophisticated multi-drug combinations, the primary challenge lies in identifying the optimal biological dose—the point where efficacy is maximized without subjecting patients to unnecessary toxicity. Because modern targeted therapies and immunotherapies often display non-linear response curves, the traditional assumption that the highest dose is the most effective is increasingly obsolete.

Navigating these complexities requires the integration of model-informed drug development and advanced exposure-response simulations. These analytical tools allow research teams to account for intricate drug-drug interactions and diverse patient populations while satisfying evolving regulatory expectations. Mastering these statistical and operational frameworks is essential for designing efficient clinical trials that prioritize patient safety and long-term treatment success in the era of precision medicine.