ctMoniTR Project

As treatments continue to improve, clinical trials that use overall survival as an endpoint become longer, which may delay new safe and effective drugs from getting to patients. To overcome this, the Accelerated Approval pathway allows for approval based on an intermediate endpoint that is reasonably likely to predict response to treatment. Circulating tumor DNA (ctDNA) is fragments of DNA shed from cancer cells, found in the bloodstream, and collected using a blood draw. Change in ctDNA levels on treatment has the potential to be used as an intermediate endpoint, however, aggregate data analyses are necessary to ensure the field is confident with using ctDNA as an intermediate endpoint.

Several organizations have performed clinical trials exploring whether change in ctDNA levels on treatment associates with overall survival in cancer, however, these have been small studies which limit the analyses and conclusions that can be drawn. To leverage the data from multiple studies for robust evidence generation, it is critical that these data are aligned to ensure measurement of ctDNA is cohesive and consistent across groups.

Friends leads a multi-stakeholder research project, ctMoniTR, with pharmaceutical companies, diagnostic labs, government health officials, patient advocates, and academic researchers. We collect data from clinical trials that incorporate ctDNA as a tool to track how advanced disease responds to treatment. Our collaboration with the statisticians at Cancer Research And Biostatistics (CRAB) assesses whether ctDNA change reflects response to treatment across multiple clinical trials. By combining efforts and aggregating data across multiple trials, we will be able to generate the evidence necessary to characterize ctDNA as an indicator of response faster than if any single organization tried to do so alone.

Step 1 of ctMoniTR aggregated five studies in patients with advanced non-small cell lung cancer (aNSCLC) treated with immunotherapy. Friends collaborated with our partners to identify these studies, create a plan to analyze the data, and perform the analysis. Findings showed robust and consistent associations between change in ctDNA levels and overall survival. Importantly, this work demonstrated that an initiative to harmonize clinical trials to measure ctDNA is possible.

Step 2 of the project expands the scope of this research to study the relationship between ctDNA and clinical outcomes across several clinical settings, drug classes, and cancer types. Initial findings from an analysis of 8 clinical trials of patients with aNSCLC treated with a tyrosine kinase inhibitor (TKI) build on Step 1 and shows that ctDNA clearance on treatment associates with improved overall survival.

Friends also leads a coordinated effort to apply findings from the ctMoniTR project and identify the evidence necessary to support use of ctDNA as an intermediate endpoint in drug development and regulatory decision-making.

Accelerated Approval allows effective treatments get to patients sooner and using ctDNA as an intermediate endpoint would reduce burdens on patients in clinical trials. ctDNA can be assessed through a blood draw, potentially allowing for measurement of a patient’s molecular response to therapy earlier, using a method that is less invasive for patients, and more frequently than radiographic response assessments. Moving an approach like this from concept to use in prospectively designed clinical trials would take substantially longer without Friends coordination and support from collaborative sponsors.