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Abstract:
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The current explosion of targeted and immunotherapeutic agents for cancer treatment has challenged statisticians to reconsider early-phase designs previously developed for cytotoxic agents. The goal of determining the maximum tolerated dose (MTD) is 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. 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. Yet, there is still much confusion about how and which biological endpoints to incorporate for determining the optimal dose for subsequent trials.
In this presentation, we provide a brief review and discussion of the latest early-phase designs proposed for targeted and immunotherapy agents. Additionally, we illustrate a novel two-stage design inspired by an adoptive T-cell therapy trial where dose-selection is driven by both toxicity and continuous immunological outcomes.
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