Abstract:
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Dose finding studies, in general, aims at determining the maximum tolerated dose (MTD) reflecting the desire to treat patients who have limited options under the assumption that higher drug doses will have better therapeutic activity. With the recent development of targeted therapy and immunotherapy, the traditional dose finding paradigm may not be optimal and targeted drug efficacy may be achieved at lower doses than the MTD. Considering such paradigm, how can we integrate more robust, patient centric dose optimization strategies and the urgency in bringing new drugs to patients faster? We are proposing new approaches and important factors are the mechanism of action of the molecule and its therapeutic index. If the therapeutic index is narrow and dose/efficacy is not plateauing the MTD paradigm is still valid. In addition, if there is a subset of patients who are tolerating well the recommended dose, they may benefit from dose increase. Conversely, if the therapeutic index is wide and dose/efficacy relationship is uncertain some novel designs that jointly model toxicity and efficacy could be considered. In this talk, we will discuss the current challenges and make proposals
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