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Wednesday, September 25
Wed, Sep 25, 2:45 PM - 4:00 PM
Thurgood Marshall West
Trial Design and Decision-Making of Early Oncology Development in the Era of Immune-Oncology

Time-to-event Bayesian Optimal Interval Design to Accelerate Phase I Trials (301031)

Daniel Li, Juno Therapeutics 
Ruitao Lin, Department of Biostatistics, The University of Texas MD Anderson Cancer Center 
Lei Nie, FDA 
Katherine E. Warren, Center for Cancer Research, National Cancer Institute 
*Ying Yuan, MD Anderson Cancer Center 

Late-onset toxicity is common for novel molecularly targeted agents and immunotherapy. It causes major logistic difficulty for existing adaptive phase I trial designs, which require the observance of toxicity early enough to apply dose escalation rules for new patients. The same logistic difficulty arises when the accrual is rapid. We propose the time-to-event Bayesian optimal interval (TITE-BOIN) design to accelerate phase I trials by allowing for real-time dose assignment decisions for new patients while some enrolled patients’ toxicity data are still pending. Similar to the rolling six design, the TITE-BOIN dose escalation/de-escalation rule can be tabulated before the trial begins, making it transparent and simple to implement, but is more flexible in choosing the target DLT rate and has higher accuracy to identify the MTD. Compared to the more complicated model-based time-to-event continuous reassessment method (TITE-CRM), the TITE-BOIN has comparable accuracy to identify the MTD, but is simpler to implement with better overdose control. A numerical study shows that the TITE-BOIN design supports continuous accrual, without sacrificing patient safety nor the accuracy of identifying the MTD, and therefore has great potential to accelerate early phase drug development.

Reference: Yuan, Y., Lin, R., Li, D., Nie, L., and Warren K. (2018) Time-to-event Bayesian Optimal Interval Design to Accelerate Phase I Trials. Clinical Cancer Research, 24, 4921-4930.