Introduction
cancer, FIP, ICH
MALIGNANCIES, CANCER, FIP
The first-in-patient (FIP) nonclinical safety package is designed to enable an initial risk assessment of the drug candidate, identify appropriate clinical safety monitoring, and define the recommended starting dose (RSD) for the FIP clinical trial. The FIP trial for oncology agents is generally conducted in patients with advanced malignancies, which necessitates careful selection of the RSD to be sufficiently safe, while also potentially providing therapeutic benefit to late-stage cancer patients with limited therapeutic options that enrolled in these trials. Therefore, an optimal balance between safety and clinical benefit is desired, such that the number of patients in initial and subsequent cohorts exposed to potential sub-optimal therapeutic doses of the investigational agent is minimized [Currently, the RSD approach for small molecule oncology agents is detailed in the International Council for Harmonisation (ICH) S9 guidance [Selection of starting dose for clinical trials depends on population (healthy volunteers or patients) and mechanism of action. Prior scientific publications have reviewed the potential approaches to determine the FIP starting dose, with authors generally focusing on the previously described toxicology-based STDA review of 59 approved small molecule oncology MTAs [Since the FIP starting dose for oncology therapeutics is now based on the ICH S9 guidance (or similar guidance from [