ctMoniTR Project
ctDNA for Monitoring Treatment Response Project
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Can changes in ctDNA be used as an early endpoint for regulatory decision-making?
What is the unmet need and why does it matter?
As treatments continue to improve, clinical trials that use overall survival (OS) as an endpoint take 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. Changes in circulating tumor DNA (ctDNA) levels have the potential to be used as an early endpoint, however, aggregate data analyses are necessary.
How is Friends helping to find solutions?
For ctDNA to be used as an early endpoint, the U.S. Food and Drug Administration (FDA) expects that patient- and trial-level meta-analyses demonstrate the association between changes in ctDNA levels and improved OS. Friends leads the ctMoniTR Project, a multi-stakeholder collaboration with pharmaceutical companies, diagnostic developers, government health officials, patient advocates, and academic researchers.
Friends collects and aggregates patient-level data from previously completed clinical trials to perform meta-analyses. By combining efforts and aggregating data across multiple trials, Friends is generating the necessary evidence to characterize changes in ctDNA as an early endpoint.
To date, the focus has been on how changes in ctDNA are associated with long-term clinical outcomes. A pilot project aggregated five studies of patients with advanced non-small cell lung cancer (aNSCLC) treated with immunotherapy and showed that decreases in ctDNA were associated with improved OS and progression-free survival (PFS). This foundational work also demonstrated that an initiative to harmonize clinical trials to measure ctDNA is possible. The work then expanded 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), ctDNA clearance on treatment was associated with improved OS and PFS. Similarly, in an analysis of 4 clinical trials of patients with aNSCLC treated with anti-PD(L)1 and/or chemotherapy, reductions in ctDNA levels were associated with improved OS at both early (0-7 weeks after treatment initiation) and later timepoints (8-13 weeks). Overall, Friends has shown that changes in ctDNA levels show promise as an early endpoint for predicting OS.
Friends’ current work focuses on building the necessary evidence 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 change as an early endpoint has the potential to do so faster and more efficiently. ctDNA change 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 reach 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 presentation in August. An event recap can be found here.
Project 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 Advocates, Genentech, Inc., Genmab, Guardant Health, Inc., Illumina, Inc., Johns Hopkins University School of Medicine, Loxo@Lilly, MD Anderson Cancer Center, Merck & Co., Inc., Molecular Characterization Laboratory (MoCha) at Frederick National Laboratory, Natera, Inc., NMD Group LLC, Novartis AG, Pfizer, Inc., Princess Margaret Cancer Centre, Regeneron Pharmaceuticals, Inc., Roche Diagnostics, Takeda Pharmaceutical Company, the U.S. Food and Drug Administration (FDA), and Xencor.