Cancer treatments have changed dramatically over the past decade, but have our dose-finding strategies kept pace?

In this episode, I speak with Dr. Ayon Mukherjee, who leads statistical innovation in early oncology development at Eli Lilly. Together, we explore Project Optimus, the FDA initiative that is changing how we think about dose optimization in oncology.

Instead of simply finding the highest dose patients can tolerate, Project Optimus encourages us to identify the dose that provides the best balance between efficacy, safety, pharmacokinetics, pharmacodynamics, and long-term tolerability.

Ayon explains why the traditional maximum tolerated dose approach worked well for chemotherapy but often falls short for targeted therapies and immunotherapies. We also discuss how statisticians can help lead this transformation by designing better dose optimization studies and collaborating more effectively with clinicians, pharmacologists, and regulators.

Why Listen to this Episode:

• Understand what Project Optimus is and why it is transforming oncology drug development.
• Learn why the traditional maximum tolerated dose (MTD) approach is no longer sufficient for many targeted therapies and immunotherapies.
• Discover how statisticians can use PK/PD, exposure-response, efficacy, safety, and tolerability data to support better dose optimization.
• Explore the progress the industry has made since Project Optimus was launched and the challenges that remain.
• Gain practical insights on collaborating effectively with clinicians, pharmacologists, regulators, and academic partners.
• Find out what statisticians can do today to help advance innovative dose optimization strategies and improve patient outcomes.

Episode Highlights

• 00:00 – Introduction to the episode
• 01:31 – Ayon Mukherjee introduces himself and his work in early-phase oncology and dose optimization.
• 02:58 – What is Project Optimus, and why did the FDA introduce it?
• 03:28 – Why traditional chemotherapy dose-finding approaches no longer fit modern targeted therapies and immunotherapies.
• 05:21 – The key principles of Project Optimus: balancing efficacy, safety, PK/PD, and long-term tolerability.
• 08:14 – The types of data needed to support dose optimization beyond dose-limiting toxicities.
• 09:40 – How far has the industry come since Project Optimus launched in 2021?
• 11:06 – Why communication and cross-functional collaboration are essential for successful implementation.
• 13:29 – Regulatory acceptance and the gap between published methodologies and industry adoption.
• 15:27 – The value of industry-academia collaboration and cross-company working groups.
• 16:53 – Why education and training are critical for increasing awareness and adoption.
• 20:06 – Open-source tools, R Shiny applications, and practical resources for implementing innovative trial designs.
• 23:23 – Final thoughts on how statisticians can improve dose optimization and ultimately serve patients better.

Links and Resources

• Connect with Dr. Ayon Mukherjee on LinkedIn
• FDA Project Optimus – An initiative from the FDA Oncology Center of Excellence to reform dose optimization in oncology drug development.
• TrialDesign.org – Open-source tools and R Shiny applications for innovative clinical trial designs.
• Innovative Design Scientific Working Group (IDSWG) – A collaborative group advancing innovative clinical trial designs in early-phase oncology.