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Optimizing Early Clinical Investigations by Increasing Predictive Value of Non-Clinical Activities

Presentation Title: Optimizing Early Clinical Investigations by Increasing the Predictive Value of Non-Clinical Activities Session 4: Beyond Surrogate Endpoints: Other Ways Translational Science Can Support Drug Development Speaker: Estelle Marrer-Berger, PhD Summary: Certain immunological therapy targets are exclusively human, making animal models impossible. New Approach Methodologies have informed a patient-centric approach, which uses human primary cells from patients and healthy donors to model the clinical response to therapies in vitro and ex vivo over a broad time course. In this case study, the models were successfully used to define a therapeutic index, minimize risk, and improve starting dose selection in a T-cell bispecific antibody therapy in Wilms Tumor 1 in Acute Myeloid Leukemia. Key Takeaways: • New In vitro techniques have enabled more detailed (cell-specific) toxicity testing of oncology treatments before beginning clinical trials • Patient-centric MABEL (minimum anticipated biological effect level) framework is of high predictive value for the estimation of the pharmacologically active dose range o Instead of predicting safe dosage using the most sensitive tumor cell line, using cells from patients and healthy donors allows investigators to reach a safe, therapeutic dosage. Using T-cell activation from the tumor line cell allows for a safe and potentially lower therapeutic dose.