All Times EDT
Keywords: Immunotherapy; MTA; Late-onset DLT; BOIN;
As molecularly targeted agents (MTAs) and immunotherapies have widely demonstrated delayed toxicity profile after multiple treatment cycles, the traditional phase I dose-finding designs may not be appropriate anymore because they just account for the acute toxicities occurring in the early period of treatment. When the dose-limiting toxicity (DLT) assessment window is prolonged to account for late-onset DLTs, it will cause logistic issues if the enrollment is suspended until all the DLT information is collected. In this presentation, we will share some experience in real trial conduct to monitor the late-onset DLTs. Also, from design perspective, we propose a novel framework to estimate the toxicity probability in the scenarios where some patients’ DLT information are not complete and then implement the Bayesian optimal interval (BOIN) design to make decisions on dose escalation/de-escalation. Our proposed approach maintains BOIN’s transparency by simply comparing the estimated toxicity probability with the escalation/de-escalation boundaries to decide the next dose level. The proposed approaches of design and analysis can provide an attractive option of phase I dose-finding clinical trials for molecularly targeted agents (MTAs) and immunotherapies, which need to account for late-onset DLT monitoring.