Assessing clinical response in early oncology development with a predictive biomarker.

In early oncology clinical trials there is often limited data for biomarkers and their association with response to treatment. Thus, it is challenging to decide whether a biomarker should be used for patient selection and enrollment. Most evidence about any potential predictive biomarker comes from preclinical research and, sometimes, clinical observations. How to translate the preclinical predictive biomarker data to clinical study remains an active field of research. Here, we propose a method to incorporate existing knowledge about a predictive biomarker - its prevalence, association with response and the performance of the assay used to measure the biomarker - to estimate the response rate in a clinical study designed with or without using the predictive biomarker. Importantly, we quantify the uncertainty associated with the biomarker and its predictability in a probabilistic model. This model estimates the distribution of the clinical response when a predictive biomarker is used to select patients and compares it to unselected cohort. We applied this method to two real world cases of approved biomarker-guided therapies to demonstrate its utility and potential value. This approach helps to make a data-driven decision whether to select patients with a predictive biomarker in early oncology clinical development.