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Abstract:
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Oncology drug development is quite different from drug development in other therapeutic areas. Phase I oncology dose-ranging trials enroll actual patients rather than healthy volunteers. The objective of phase 1 trials with those compounds was to administer the highest doses possible in order to determine the maximum tolerated dose (MTD). But in current times the objectives shift from the definition of an MTD to the evaluation of a recommended phase 2 dose (RP2D), since targeted therapies and even chemotherapeutic agents do not necessarily require the highest possible dose to be efficacious for target modulation and clinical activity. In search of a safe and efficacious dose, we have proposed a benefit-risk Analysis where we used all the available evidences. In this analysis, we used dose-safety model to determine maximum dose with an acceptable toxicity rate and dose-efficacy model to determine a minimum dose with a desired efficacy.We modeled exposure with dose to obtain probabilities of the active and safe dose levels that are within the pre-defined optimum exposure levels. Integrating all aforementioned results, we recommend the safe dose ranges for further development.
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