US Food and Drug Administration embraces using innovation to identify optimized dosages for patients with cancer

Translational strategies that iteratively evaluate emerging data should be considered to increase the likelihood of identifying dosages that optimize the long-term benefits and maintain the quality of life of all patients with cancer. INNOVATIVE TRIAL DESIGN AND ANALYSES Alternative trial designs and analytical methods with an iterative process that leverages nonclinical data and clinical observations beyond short-term safety data are needed to identify optimized dosages for newer oncology drugs, given targeted therapies and immunotherapies often do not demonstrate traditional DLTs and meaningful clinical activity may be observed at dosages lower than the MTD. 4 Controlled backfill, 5 strategically planned expansion cohorts, and randomized parallel dosage comparisons can yield additional clinical data to increase confidence that dosages carried forward into registration trials have been optimized. [...]recent data suggest mechanistic modeling and simulation (quantitative systems pharmacology in particular) is being used to inform a wide range of clinical trial designs, clinical development, and regulatory decisions for immunotherapies, including for dosage optimization and biomarker selection. 9 As an example, a quantitative systems pharmacology modeling platform that was built to describe complex interplay among immune cells, cancer cells, immunotherapy, and other relevant factors is being used to evaluate various immunotherapy combinations to predict patient outcomes in virtual trials. 10 Finally, once a new drug is approved, it is often then used in populations that are much more heterogeneous than the population studied in the clinical trials that supported its approval. [...]our office leads the Center for Drug Evaluation and Research (CDER) MIDD Paired Meeting Program, 11 which continues to advance and integrate development and application of exposure-based, biological, and statistical models in drug development and regulatory review.