All Times EDT
Keywords: ctDNA, Biomarkers, Early Endpoints
Circulating tumor DNA (ctDNA) has promise for tracking tumor dynamics including evaluating treatment response, monitoring residual disease, and selecting patient populations. Friends of Cancer Research (Friends) with statistical and data management support from Cancer Research and Biostatistics (CRAB) established a consortium of drug developers, assay developers, regulators, and academics to collaboratively analyze multiple clinical trial datasets to answer the question: Do changes in ctDNA reflect response to treatment? The ctDNA for Monitoring Treatment Response (ctMoniTR) Project initially focused on data from 5 independent clinical trials including patients with lung cancer treated with PD(L)1 inhibitors (Step 1) and found consistent association between reductions in ctDNA and improved treatment outcomes. Step 2 of the ctMoniTR project is underway with clinical trials that include more patients, more treatments, and more cancer types. In tandem, Friends has worked with cross-industry stakeholders to identify clinical, statistical, and technical barriers to implementing ctDNA as an early endpoint and develop an evidentiary roadmap to support standardized approaches for implementing and evaluating ctDNA as an early endpoint in drug development. A key component of the evidentiary roadmap is appropriate statistical approaches to analyze multiple trials in a meta-analysis, while also considering how these findings and approaches will inform future drug development and ctDNA use. Our roundtable will seek input on key statistical considerations to analyzing ctDNA dynamics and explore challenges and opportunities for the use of meta-analysis approaches to enable cross study evaluations and evaluation of a novel endpoint.