CRM and partial order CRM with adaptive rescaling for dose‐finding in immunotherapy trials with a continuous outcome

Abstract

In many phase 1 oncology trials of immunotherapies, no dose‐limiting toxicities are observed and the maximum tolerated dose cannot be identified. In these settings, dose‐finding can be guided by a biomarker of response rather than the occurrences of dose‐limiting toxicity. The recommended phase 2 dose can be defined as the dose with mean response equal to a prespecified value of a continuous response biomarker. To target the mean of a continuous biomarker, we build on the idea of the continual reassessment method and the quasi‐Bernoulli likelihood. We extend the design to a problem of finding the recommended phase 2 dose combination in a trial with multiple immunotherapies.