ctDNA for Monitoring Treatment Response Project
Diagnosing and understanding how cancer responds to treatment can be challenging due to limits in technology (e.g., imaging). Circulating tumor DNA (ctDNA) is fragments of DNA shed from cancer cells, found in the bloodstream and collected using a blood draw.
Emerging science demonstrates ctDNA may be useful for diagnosing and tracking a patient’s cancer. However, before ctDNA measurement is used in clinical practice and for regulatory decisions, additional evidence needs to be generated. That’s where Friends comes in.
Several organizations have performed clinical trials exploring a range of uses of ctDNA 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 several 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) is helping to determine whether ctDNA changes reflect 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 focused on a few studies in patients with non-small cell lung cancer (NSCLC) 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 changes in ctDNA and patient outcomes. 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.
Friends also leads a coordinated effort to apply findings from the ctMoniTR project and identify the evidence necessary to support use of ctDNA as a surrogate endpoint in drug development and regulatory decision-making. Our efforts will expand outside of advanced disease to understand the value of monitoring ctDNA in earlier stages of cancer. Ultimately, these efforts will provide consensus around how ctDNA can be used to inform treatment decisions, support drug development, and inform regulatory decision-making.
The ctMoniTR project will help validate whether blood biomarkers, such as ctDNA, can be used to easily and more rapidly determine whether a drug is working. By getting this information quickly and in a less invasive way, physicians and patients will understand if the treatment is working or if they should change treatments. Moving an approach like this from concept to clinical use would take a lot longer without Friends coordination and support from collaborative sponsors.
- The ctMoniTR project builds off Friends’ previous work in the field, including the Friends Annual Meeting 2018 whitepaper. We also discussed this topic at our annual meeting in 2021, focusing on key considerations for expanding the work into early stage disease.
- Findings from ctMoniTR Step 1 were presented in July 2020 and a question and answer session was held following that event in August 2020. An event recap can be found here. A manuscript of findings was published in JCO Precision Oncology.
- Step 2 of ctMoniTR launched in 2021.
- In July 2022, our working group presented the evidentiary roadmap in a public meeting discussing the use of ctDNA as an early endpoint.
- In October 2022, Friends presented a poster at the 4th Annual ISLB Congress about the ctMoniTR Project.
- In June 2023, Friends presented a poster at the ASCO Annual Meeting.
- In July 2023, Friends hosted a meeting to share initial data from the Baseline ctDNA Project and results from ctMoniTR Step 2 Module 1 as well as discussed regulatory considerations for using ctDNA as an early endpoint.
ctMoniTR Step 1 Partners: AstraZeneca, Bristol Myers Squibb, Genentech, Inc., Guardant Health, Inc., Johns Hopkins University School of Medicine, LexentBio, Inc. (now Foundation Medicine, Inc.), Merck & Co., Inc., the NMD Group LLC, Penn Medicine, Roche Diagnostics, and the U.S. Food and Drug Administration (FDA)
ctMoniTR Step 2 Partners: Agilent Technologies, AstraZeneca, Bayer, Biodesix, Bio-Rad Laboratories, Inc., Boehringer Ingelheim, Bristol Myers Squibb Company, Cancer Research And Biostatistics (CRAB), Clovis Oncology, Inc., EMD Serono, Inc. (Merck KGaA), European Organisation for Research and Treatment of Cancer (EORTC), Foundation Medicine, Inc., Genentech, Inc., Guardant Health, Inc., Gritstone Bio, Inc., Illumina, Inc., Johns Hopkins University School of Medicine, Loxo@Lilly, MD Anderson Cancer Center, Molecular Characterization Laboratory (MoCha) at Frederick National Laboratory, Natera, Inc., NMD Group LLC, Novartis AG, Pfizer, Princess Margaret Cancer Centre, Regeneron Pharmaceuticals, Inc., Roche Diagnostics, Takeda Pharmaceutical Company, the U.S. Food and Drug Administration (FDA), and Xencor