A Bayesian design for finding optimal biological dose with mixed types of responses of toxicity and efficacy

For molecularly targeted therapy and immunotherapy, the targeted dose in the early phase clinical trial has been shifted from the maximum tolerated dose for the cytotoxic drug to the optimal biological dose where both toxicity and efficacy are considered. In this paper, we consider the situation that the responses of toxicity and efficacy are mixed in binary and continuous types, respectively, where the continuous endpoint bears more magnitude information than the binary endpoint after dichotomization. We propose combining two model-based designs to sequentially identify the most efficacious and tolerably safe dose. The employed designs both take the dose level information into account to achieve high estimation efficiency. We demonstrate the superiority of the proposed method to some existing methods by simulation.