​​​​​​​​FDA-AACR: Oncology Dose-finding Workshop

​June 13, 2016 | ​​Walter E. Washington Convention Center, Washington, D.C.

​Co-sponsored by the FDA and the AACR    

Slide/audio recordings and transcripts are now available.​​​

Workshop paper published in Clinical Cancer Research.


Given the recent history of approvals based on the results of early phase trials driven by extraordinary efficacy data, the incentive for conducting rigorous dose-finding trials may not be overtly apparent. However, the increasing need for the development of combination therapy due to resistance to monotherapy and poor tolerance of approved dosing regimens underscores the need for a more efficient process of dose selection in the early stages of study design. 


With the success of the 2015 FDA-AACR Dose Finding of Small Molecule Oncology Drugs Public Workshop​, we are pleased to announce the 2016 FDA-AACR Dose Finding Workshop. This year we will broaden the discussion scope to all oncology drugs and focus the theme of the workshop towards drug efficacy. Recent approvals of nivolumab, osimertinib, and pembrolizumab highlight novel dose-finding strategies employed in each respective development program. An interdisciplinary presentation surrounding these development programs along with expert commentary and robust discussion is planned, with particular focus on: exposure-response relationships, modeling and simulation for dose finding, non-clinical models for efficacy, and design for dose-optimization studies.​   

Workshop Agenda, Bios, and Presentation Slides 

View/download transcript - Session Ia
View/download transcript - Session Ib
View/download transcript - Session I panel
View/download transcript - Session II
View/download transcript - Session III

Slide/audio recording - Session Ia
Slide/audio recording - Session Ib
Slide/audio recording - Session I panel
Slide/audio recording - Session II
Slide/audio recording - Session III

Welcome and Workship Objectives
8 - 8:05 a.m.

Workshop Co-chairs

Pasi Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology; scientific director, Belfer Institute for Applied Cancer Science; senior physician, Dana Farber Cancer Institute and professor of medicine, Harvard Medical School

Geoffrey Kim, MD, director, Division of Oncology Products I (DOP1), Office of Hematology and Oncology, Center for Drug Evaluation and Research, FDA

Amy McKee, MD, deputy officer director (acting), Office of Hematology and Oncology Products​, Center for Drug Evaluation and Research, FDA

Eric Rubin, MD, vice president and therapeutic area head, Oncology Early Clinical Development, Merck Research Labs

SESSION I: Exposure-response Relationships and Medeling and Simulation for Dose-finding
8:05 - 11:45 a.m.

Session Chair: Geoffrey Kim, MD - FDA

Goals for session:

  • To discuss prior methodologies to determine exposure-response (E-R) and lessons learned from past examples
  • To define and identify key “best practices” of E-R analyses and methodologies to conduct these types of analyses
  • To discuss optimal uses of E-R relationships in dose finding and optimization

Dinesh De Alwis, PhD – Merck Research Labs
Shruti Agrawal, PhD – Bristol-Myers Squibb
Chyi-Hung Hsu, PhD - Johnson & Johnson
​Gabriel Helmlinger, MD, PhD – AstraZeneca
Diane Wang, PhD – Pfizer

Additional Panelists (in alphabetical order):
Kelvin Dickenson – Patient Representative
Jin Jin, PhD – Genentech
Sumithra Mandr​ekar, PhD - Mayo Clinic
Lillian Siu, MD – Princess Margaret Hospital, University of Toronto
Yaning Wang, PhD - FDA

Top of page​​

SESSION II: Non-clinical Models Used for Go/No-go Decisions
12:50 - 2:35 p.m.

Session Chair: Todd Palmby, PhD - FDA

Goals for session:

  • To discuss the state of the science in non-clinical efficacy models
  • To discuss best practices in target validation or lead selection based on non-clinical efficacy models
  • To discuss the state of the science in PK-PD modeling to translate non-clinical tumor accumulation characteristics and identify a minimum target plasma concentration in patients

Darren Cross, PhD - AstraZeneca
Chandni Valiathan, PhD – Merck Research Labs
Alan Korman, PhD – Bristol-Myers Squibb
Juliet Williams, PhD - Novartis Institutes for Biomedical Research​

Additional Panelists (in alphabetical order):
Hans Loland – Patient Representative
Thomas Jaki, PhD - Lancaster University
Mark Ratain, M​D – University of Chicago
Amit Roy, PhD – Bristol-Myers Squibb
Karthick Vishwanathan, PhD – AstraZeneca​

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​​​​SESSION III: Designs for Dose Optimization Studies: Pre-market and Post-market
2:50 - 4:50 p.m.

Session Chair: Eric Rubin, MD - Merck

Goals for session:

  • To discuss the starting dose and design strategies to minimize exposure of patients to potentially ineffective or toxic/intolerable doses
  • To discuss best practices for dose selection studies and dose optimization studies using novel approaches such as expansion of multiple dose cohorts and adaptive designs
  • To discuss best practices for dose optimization of combination studies
  • To discuss the ideal design for a post-market dose optimization study

Haleh Saber, PhD – FDA
Pasi Jänne, MD, PhD – Dana Farber Cancer Institute
Ying Lu, PhD –VA Cooperative Studies Program and Stanford University
Chao Liu, PhD - FDA
Matthew Guo, PhD – Eisai​

Additional Panelists (in alphabetical order):
Kelvin Dickenson – Patient Representative
Serban Ghiorghiu, MD – AstraZeneca
Hans Loland – Patient Representative
Sumithra Mandrekar, PhD – Mayo Clinic
Lei Nie, PhD – FDA
Nam Atiqur Rahman, PhD – FDA
Lillian Siu, MD – Princess Margaret Hospital, University of Toronto

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Wrap-up Discussion
4:50 - 5 p.m.

Workshop Co-chairs

5 p.m.

​This workshop ​is a follow-up to the successful FDA-AACR public workshop: Dose-finding of Small Mole​cule Oncology Drugs, which was ​held May 18-19, 2015. Full transcripts and select presentations from that workshop are also ​available.