Designing Dose-Optimization Studies in Cancer Drug Development: Discussions with Regulators

Abstract

The article provides a summary of discussions from the American Statistical Association (ASA) Biopharmaceutical (BIOP) Section Open Forums on March 18th, June 10th, and July 8th of 2021, organized by the ASA BIOP Statistical Methods in Oncology Scientific Working Group in coordination with the U.S. Food and Drug Administration (FDA) Oncology Center of Excellence and the LUNGevity Foundation. Diverse stakeholders including oncologists, patient advocates, experts from regulatory agencies across the world, academicians, and representatives from the pharmaceutical industry engaged in a lively discussion on strategies for and designs of dose-optimization studies in cancer drug development. Dose-optimization is one of the major challenges in oncology drug development. The discussions were focused on considerations in designing dose-optimization studies of products for treatment of cancer patients in pre-approval and post-approval stages. Presenters and panelists discussed diverse ideas and methods and agreed that a shift in paradigm is required in oncology drug development that should improve dose optimization while not unnecessarily delaying patient access to potentially efficacious new treatments.

Keywords:

• DLT
• Dose-optimization
• MTD
• Oncology drug development

Acknowledgments

Authors thank Joan Todd (FDA) and Rick Peterson (ASA) for supporting the forum and Dr. Jianchang Lin (Takeda), Dr. Suman Sen (Novartis), and Dr. Nicole Li (Merck) for taking the meeting minutes.

Disclosure Statement

No potential competing interest was reported by the authors. This publication reflects the authors’ views. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein. The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agency/agencies or organizations with which the authors is/are employed/affiliated.

Additional information

Funding

Martin Posch is a member of the EU Patient-centric clinical trial platform (EU-PEARL). EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement N^∘ 853966. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Children’s Tumor Foundation, Global Alliance for TB Drug Development nonprofit organization, Springworks Therapeutics Inc.