Emily V. Dressler, PhD, Biostatistics and Bioinformatics Shared Resource Facility, Markey Cancer Center, University of Kentucky

"Early phase development in clinical trials: What have we accomplished and where do we need to go?"

The current explosion of new targeted and immunotherapeutic agents for cancer treatment has challenged statisticians to reconsider early phase designs previously developed for cytotoxic agents. In the new therapeutic landscape, the goal of determining the maximum tolerated dose (MTD) may be no longer desirable because novel agents are characterized by a reduced toxicity profile, to the point of being essentially safe within the therapeutic dose range. Moreover, for targeted agents, the relationship between target effect and toxicity might not be linear, implying that the most efficacious dose might be below the MTD. Under these circumstances dose selection should not be based solely on toxicity but also examine both toxicity and activity. Recent phase I trials for single-agent or combination therapy have focused on detecting signals of antitumor activity, pharmacokinetic/pharmacodynamics (PK/PD) relationships, or on assessing feasibility and utility of biological correlative assays. This talk will focus on current designs, specifically the continual reassessment method and its variations, and discuss areas for improvement and growth to address these modern considerations.

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