The FDA has granted breakthrough device designation for the Haystack MRD® test, a circulating tumor DNA (ctDNA) liquid biopsy, designed to identify patients with stage II colorectal cancer (CRC) who are minimal residual disease (MRD) positive and may benefit from adjuvant therapy following curative-intent surgery.1
The Haystack MRD test is intended to detect MRD by uncovering trace fragments of tumor-derived DNA circulating in the bloodstream. These fragments can indicate residual, recurrent, or treatment-resistant disease, enabling clinicians to identify patients who are ctDNA-positive after surgery and guide adjuvant treatment decisions in accordance with approved product labeling.
Developed by leaders in cancer genomics and liquid biopsy innovation, Haystack MRD is a highly sensitive and specific assay optimized for detecting very low levels of ctDNA. Its clinical utility has been demonstrated in multiple trials and research collaborations with major institutions across the United States, Canada, and Australia, including the pivotal phase 2 DYNAMIC study (ACTRN12615000381583).2 The test is already being used by clinicians at more than 75 leading cancer centers, academic institutions, and health systems as a part of multiple clinical trials and research studies.1
“We are committed to working with the FDA and our research partners to validate the use of Haystack MRD in a variety of solid tumors, building on this first designation for an early-stage CRC,” Dan Edelstein, vice president and general manager of Haystack Oncology, stated in a news release. “Our goal is to deliver highly accurate, personalized monitoring of treatment response and recurrence to more patients, both in clinical care and in pharmaceutical trials, and this breakthrough designation brings us closer to our goal.”
DYNAMIC Study Breakdown
The study enrolled 455 patients with stage II colon cancer who were randomized in a 2:1 ratio to either a ctDNA-guided strategy (n = 302) or standard clinicopathological assessment (n = 153).2 In the ctDNA-guided arm, adjuvant therapy decisions were based exclusively on ctDNA testing performed on blood samples collected at 4 and 7 weeks after surgery. Patients with detectable ctDNA at either time point were treated with adjuvant therapy, and those with undetectable ctDNA did not receive systemic therapy.
In the standard-of-care arm, treatment allocation followed conventional clinicopathological risk factors, including tumor size, grade, and lymph node assessment. Patients deemed high risk received adjuvant treatment. This design allowed direct comparison between biomarker-driven and traditional approaches to post-surgical therapy selection.
This pivotal trial demonstrated that chemotherapy use was significantly reduced in the ctDNA-guided group at 15% compared with 28% in the standard-of-care group. Importantly, this reduction in systemic therapy exposure did not compromise efficacy: 2-year recurrence-free survival (RFS) was comparable between both strategies.
Plans for Future Analysis
In stage III CRC, adjuvant therapy is standard for nearly all patients; however, the intensity and duration of treatment often rely on clinicopathologic features, which may lead to over- or under-treatment. The ongoing phase 2/3 DYNAMIC-III trial (ACTRN12617001566325) is evaluating whether ctDNA can refine treatment intensity by identifying patients who may benefit from de-escalation strategies and those who may require escalation.3 Patients with resected stage III colon cancer who are fit for adjuvant chemotherapy are being randomly to receive ctDNA-informed treatment guidance vs standard-of-care management. In the ctDNA arm, patients with a positive ctDNA test 5 or 6 weeks after surgery are receiving escalated therapy; rather than single-agent fluoropyrimidine or an oxaliplatin-based doublet, patients are being escalated from 3 months of the doublet to 6 months or FOLFOXIRI, or from 6 months of the doublet to FOLFOXIRI.
In ovarian cancer, where diagnosis frequently occurs at advanced stages, ctDNA is being studied as a dynamic prognostic marker in the DYNAMIC-ovarian trial.1 Investigators are assessing ctDNA at multiple time points—including prior to therapy initiation, during treatment, and after completion of therapy—in both neoadjuvant and adjuvant settings. This study may clarify whether ctDNA can serve as an early indicator of treatment response and long-term outcomes in this aggressive malignancy.
References
- FDA grants breakthrough device designation for haystack mrd circulating tumor dna test from quest diagnostics. News Release. Accessed August 29, 2025. https://www.prnewswire.com/news-releases/fda-grants-breakthrough-device-designation-for-haystack-mrd-circulating-tumor-dna-test-from-quest-diagnostics-302536229.html
- W K. Haystack MRDTM: Proven clinical utility – Haystack MRDTM. Haystack MRDTM. Published May 31, 2023. Accessed August 29, 2025. https://haystackmrd.com/haystack-mrd-proven-clinical-utility/
- Tie J, Wang Y, Loree JM, et al. Cohen ctDNA-guided adjuvant chemotherapy escalation in stage III colon cancer: Primary analysis of the ctDNA-positive cohort from the randomized AGITG dynamic-III trial (intergroup study of AGITG and CCTG). J Clin Oncol. 2025;43(suppl 16):3503. doi:10.1200/JCO.2025.43.16_suppl.3503