Probability Interval Design based on both Toxicity and Efficacy
The Probability Interval design based on both Toxicity and Efficacy (PITE) provides an efficient and powerful solution to immuno-oncology (IO) phase 1 dose finding trials. As the monotonic dose-response assumption, which is applicable for cytotoxic drugs, may not hold for IO agents, traditional phase 1 dose finding designs searching for the maximum tolerated dose (MTD) are not suitable to IO agents. PITE is a novel and transparent interval design for dose finding trials of IO agents. This design incorporates efficacy outcomes to inform dosing decisions to optimize efficacy and safety simultaneously. PITE is a perfect match to the CAR-T agents and other potential IO agents, in which the efficacy outcome (or the surrogate efficacy outcome) can be quickly observed.
- Compared to the toxicity-based designs (3+3, CRM, mTPI-2, etc.), PITE incorporates information of efficacy and therefore enables investigator to quickly assess the drug’s potency and look for the optimal biological dose (OBD), rather than MTD.
- PITE is simple, flexible and transparent, as the decision table can be pre-tabulated prior to trial initiation.