ctMoniTR Project
ctDNA for Monitoring Treatment Response Project
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Do reductions in ctDNA levels post-treatment correspond with therapeutic outcomes?
What is the unmet need and why does it matter?
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 early endpoint that is reasonably likely to predict response to treatment. Circulating tumor DNA (ctDNA) is fragments of DNA shed from cancer cells into the bloodstream that may correlate with clinical outcomes. Changes in ctDNA levels on treatment have the potential to be used as an intermediate endpoint, however, aggregate data analyses are necessary.
How are we helping to find solutions?
Several organizations have performed clinical trials exploring whether changes in ctDNA levels on treatment are associated with overall survival in cancer, however, these have been small studies which limit the analyses and conclusions that can be drawn. For ctDNA to be used as an early endpoint, FDA expects that patient- and trial- level meta-analyses demonstrate the association between decreases in ctDNA levels and improved overall survival.
Friends leads the ctMoniTR Project, a multi-stakeholder collaboration with pharmaceutical companies, diagnostic developers, government health officials, patient advocates, and academic researchers. We collect and aggregate patient-level data from previously completed clinical trials with the statisticians at Cancer Research And Biostatistics (CRAB) to assess whether changes in ctDNA levels reflect response to treatments. By combining efforts and aggregating data across multiple trials, we are the group generating the evidence necessary to characterize ctDNA as an early endpoint.
We started the project by aggregating five studies in patients with advanced non-small cell lung cancer (aNSCLC) treated with immunotherapy showing decreases in ctDNA are associated with improved OS and PFS. This foundational work also demonstrated that an initiative to harmonize clinical trials to measure ctDNA is possible. We then expanded the scope to several clinical settings, drug classes, and cancer types. In an analysis of 8 clinical trials of patients with aNSCLC treated with a tyrosine kinase inhibitor (TKI), findings showed that ctDNA clearance on treatment was associated with improved overall survival and progression-free survival. Similarly, in an analysis of 4 clinical trials of patients with aNSCLC treated with anti-PD(L)1 and/or chemotherapy, findings showed that reductions in ctDNA levels were associated with improved survival at both early (0-7 weeks after treatment initiation) and later timepoints (8-13 weeks). Overall, we have shown that ctDNA levels show promise as an early endpoint for predicting 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 early endpoint in drug development and regulatory decision-making.
How does this impact patients?
Accelerated Approval allows effective treatments to get to patients sooner and using ctDNA as an early endpoint has the potential to do so faster and more efficiently. ctDNA may be better than RECIST-based assessments, which means that fewer patients may need to be enrolled on clinical trials for a shorter amount of time to come to the same conclusions.
Project Approach
Project Outcomes
Friends prioritizes sharing findings from our projects with the public to inform policy:
Friends Led Peer Reviewed Literature
Andrews HS, Zariffa N, Nishimura KK et al. Molecular Response Cutoffs and ctDNA Collection Timepoints Influence on Interpretation of Associations Between Early Changes in ctDNA and Overall Survival in Patients Treated with Anti-PD(L)1 and/or Chemotherapy. J Immunother Cancer 2025;13(9):e012454. http://doi.org/10.1136/jitc-2025-012454.
Andrews HS, Zariffa N, Nishimura KK et al. ctDNA Clearance as an Early Indicator of Improved Clinical Outcomes in Advanced NSCLC Treated with TKI: Findings from an Aggregate Analysis of Eight Clinical Trials. Clinical Cancer Research 2025;31:2162–2172. https://doi.org/10.1158/1078-0432.CCR-24-3612.
McKelvey BA, Andrews HS, Baehner FL et al. Advancing Evidence Generation for Circulating Tumor DNA: Lessons Learned from A Multi-Assay Study of Baseline Circulating Tumor DNA Levels across Cancer Types and Stages. Diagnostics 2024;14:912. https://doi.org/10.3390/diagnostics14090912.
Vega DM, Nishimura KK, Zariffa N et al. Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients with Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors. JCO Precis Oncol 2022;6:e2100372. https://doi.org/10.1200/PO.21.00372.
Friends Supported Peer Reviewed Literature
Towards Preanalytical Best Practices for Liquid Biopsy Studies: A BLOODPAC Landscape Analysis. Lockwood CM, Merker JD, Bain E, […] Stewart M, et al. Clinical Pharmacology & Therapeutics 2024.
Liquid biopsies coming of age: biology, emerging technologies, and clinical translation- An introduction to the JITC expert opinion special review series on liquid biopsies. Stewart MD, Anagnostou V. The Journal of ImmunoTherapy of Cancer 2023.
Plasma ctDNA as a Treatment Response Biomarker in Metastatic Cancers: Evaluation by the RECIST Working Group. Wyatt AW, Litiere S, Bidard FC, […] Andrews HS, et al. Clinical Cancer Research 2024.
White Papers
Friends Public Meetings
In February 2026, Friends hosted a meeting to review the current landscape and application of evolving early endpoints such as ctDNA and explore how they may improve trial efficiency and inform regulatory decision-making.
In July 2023, Friends hosted a meeting to share initial data from the Baseline ctDNA Project and results from ctMoniTR Step 2 Module 1 and discussed regulatory considerations for using ctDNA as an early endpoint.
In July 2022, Friends hosted a public meeting to discuss the use of ctDNA as an early endpoint.
In summer 2020, Friends presented findings from ctMoniTR Step 1 in July then held a question and answer session following the findings presentation in August. An event recap can be found here.
Project Partners
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., NMD Group LLC, Penn Medicine, Roche Diagnostics, and the U.S. Food and Drug Administration (FDA).
ctMoniTR Step 2 Partners: Agilent Technologies, Inc., AstraZeneca, Bayer, Biodesix, Bio-Rad Laboratories, Inc., Boehringer Ingelheim, Bristol Myers Squibb, Cancer Research And Biostatistics (CRAB), EMD Serono, Inc. (Merck KGaA), European Organisation for Research and Treatment of Cancer (EORTC), Foundation Medicine, Inc., Friends Advisory Advocate, Genentech, Inc., Genmab, Guardant Health, 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.