Increasing complexity in oncology clinical trials raises challenges for clinical pharmacologists.
By Konstantine W. Skordos, Ph.D., Translational Clinical Oncology, Novartis Institutes for BioMedical Research
Preclinical and early clinical development in oncology are among the most challenging of any therapy area. Once potential compounds demonstrate a measure of promise with in vitro and in vivo disease models, a race begins to deliver it to patients in desperate need of new therapies. Rarely are compound properties fully explored in early trials involving healthy volunteers, historically due to safety considerations for cytotoxic agents potentially active in malignant neoplastic disease. Even in the setting of favorable safety profiles for some molecularly targeted agents, it will rarely be ethical to delay entry into patients who may benefit from the potential medicine. Additionally, patient selection may be informed by genetic screening for trials involving molecularly targeted agents. Because patients likely to respond can be identified with precision, the potential exists for very early evidence of target validation and clinical response. Therefore, trial complexity has increased dramatically with numerous endpoints including but not limited to safety, pharmacokinetics (PK), pharmacodynamics (PD), biomarkers, and of course efficacy. The nature of phase 1 trials in oncology has been provided by Wong and colleagues, which includes a robust discussion of associated challenges.1 If clinical proof of concept is achieved, confirmatory trials to support registration of the new drug are started with urgency, and clinical pharmacology studies to support the eventual label must also be started with urgency.