Novel Designs of Early Phase Trials for Cancer Therapeutics

Table of Contents

Introduction: Changing landscape of phase I trials 1. Phase I trial designs: Past, Present, and Future 2. Statistical perspectives on cohort expansions in early phase trials 3. Determining the optimal dose and schedule 4. Conducting large phase I trials with multiple expansion cohorts 5. Role and application of molecular profiling in early phase trials 6. Novel trial designs for immunotherapies 7. Designing trials for cell based therapies 8. Evaluating novel drug combinations in early phase trials 9. Integrating biomarkers in early phase trials: developing the evidence base for 'actionable' biomarkers 10. Novel imaging endpoints in early phase trials 11. Developing a novel agent: the regulatory process perspective 12. Conducting proof of concept phase I trials-Regulatory Implications 13. Efficacy endpoints in early phase trials 14. Incorporation of Patient Reported Outcomes in early phase trials

Authors

Shivaani Kummar Professor of Medicine and Radiology, Co-Director, Translational Oncology Program at Stanford, Director of the Phase I Clinical Research Program, Stanford University, USA. Upon completing her medical degree from Lady Hardinge Medical College in New Delhi, India, Shivaani Kummar moved to the United States to train in Internal Medicine at Emory University in Atlanta, Georgia. Following this Kummar was selected to pursue fellowship training at the National Institute of Health (NIH) in Medical Oncology and Hematology, which culminated in being offered a faculty position at Yale University, New Haven CT. After spending four years as Assistant Professor of Medicine at Yale Cancer Center, she moved back to the National Cancer Institute (NCI), NIH, where she developed a clinical research program in novel cancer therapeutics. In 2011 she became Head of Early Clinical Trials Development in the Office of the Director, Division of Cancer Treatment and Diagnosis, NCI. Kummar moved to Stanford University in 2015 as Professor of Medicine and Director of the Phase I Clinical Research Program. Kummar's research interests focus on developing novel therapies for cancer. She specializes in conducting pharmacokinetic and pharmacodynamic driven first-in-human trials tailored to make early, informed decisions regarding the suitability of novel molecular agents for further clinical investigation. Kummar is the principal investigator of numerous early phase trials, and serves on multiple national and international scientific committees. Chris Takimoto Chief Medical Officer, Forty Seven Inc., USA. Chris Takimoto did his undergraduate training in Chemistry at Stanford University before receiving his M.D. and Ph.D. in Pharmacology from Yale University. He subsequently completed fellowships in Medical Oncology at the National Cancer Institute (NCI) and Clinical Pharmacology at the Uniformed Services University and he then served as a Senior Investigator in the NCI's Medicine Branch. While at the NCI, Takimoto worked in the GI tumor group focusing on translational research and early phase clinical trials. In 2000, he became an Associate Professor at the University of Texas Health Science Center San Antonio (UTHSCSA), where he also held the Zachry Chair for Translational Research at the Institute for Drug Development/Cancer Therapy & Research Center. At the time, the CTRC was home to the largest oncology Phase 1 program in the world. Takimoto was also a Professor (Adjunct) of Pharmacology at UTHSCSA, and in 2007, he helped to found an independent Phase 1 oncology clinical research center called South Texas Accelerated Research Therapeutics (START). While in San Antonio he was a principal or co-investigator on over 250 early phase oncology clinical trials. In 2008, Takimoto moved to Johnson & Johnson ultimately becoming Vice President of Experimental Medicine Early Development for Oncology at Janssen R&D where he oversaw all the early phase clinical trials for the oncology portfolio. In 2016, he joined a new, clinical stage biotechnology company called Forty Seven, Inc. as Chief Medical Officer.