Market Intelligence
ctDNA SoC Countdown
Phase 3 trials are using ctDNA to make treatment decisions. The majority are in colorectal cancer, most answering one question: should this patient get chemotherapy after surgery?
The clinical research community has reached a verdict on ctDNA as a biomarker: it works. The question now being answered in Phase 3 trials is harder — should treatment decisions actually change based on ctDNA? That question, repeated across roughly two dozen pivotal trials, is what the SoC countdown is measuring.
When a Phase 3 trial reads out positive and a regulator agrees, ctDNA-guided treatment gets written into clinical guidelines. The assay that powered the trial becomes the standard. Understanding the shape of the Phase 3 pipeline — which cancers, which decisions, which sponsors — is the clearest available map of where the first commercial indications will land.
11
Phase 1
Proof of concept
102
Phase 2
Validation
26
Phase 3
Pivotal — SoC approaching
What decision is ctDNA making?
Sorted by combined P2+P3 total. De-escalation is more prominent in Phase 2 — the harder question not yet at pivotal scale.
Where is ctDNA activity concentrated?
Sorted by combined total. Lymphoma is visible in Phase 2 (Hodgkin de-escalation, DLBCL) but not yet in Phase 3.
Live from ClinicalTrials.gov · updates daily
What Phase 2 signals about the next Phase 3 wave. De-escalation trials — led by PRECISE-HL (Hodgkin lymphoma, 125 patients) and urothelial CT-READ — are the most likely Phase 3 candidates to emerge next. De-escalation in Hodgkin is particularly compelling given young patients and long-term chemo toxicity. Also notable: AbbVie entered Phase 2 with a ctDNA+ CRC trial — the first pharma-sponsored ctDNA-guided treatment study, signaling the pharma gap is beginning to close.
Why colorectal dominates. Post-surgical adjuvant chemotherapy for colon cancer affects ~150,000 US patients annually. Current staging criteria over-treat a substantial fraction — patients whose cancer was cured by surgery but who still receive six months of FOLFOX. ctDNA has a clear, binary role here: detect residual disease and treat only those who need it. Multiple academic groups in France, Germany, the US, and South Korea have independently designed Phase 3 trials around exactly this decision. When these trials read out, the market they unlock is large, well-defined, and already has a payer rationale.
Landmark trials
The five largest or highest-profile Phase 3 trials — each capable of generating a labeled indication on readout.
CIRCULATE: ctDNA-guided Adjuvant Treatment in Stage II Colon Cancer
The largest ctDNA trial in the dataset. ctDNA+ post-surgery patients receive capecitabine; ctDNA− are spared adjuvant chemo entirely. Enrollment complete — readout imminent.
COBRA: Colon Adjuvant Chemo Based on Residual Disease (NRG Oncology)
NRG Oncology — the US cooperative group gold standard — running at 1,061 sites. Signatera is the named assay. A positive readout here writes ctDNA into ASCO guidelines.
ctDNA-based Adjuvant Decision in Stage II Colon Cancer
French Phase 3: ctDNA+ → mFOLFOX6 chemotherapy; ctDNA− → active surveillance only. Pure binary decision trial — designed to generate the regulatory evidence package.
MODERN: MRD-Guided Adjuvant Therapy in Urothelial Cancer
NCI-sponsored, 498 sites. ctDNA/MRD positivity post-surgery triggers nivolumab + relatlimab vs. observation. NCI sponsorship signals this is intended to generate regulatory-grade evidence.
PRODIGE 88: Chemo in ctDNA+ Stage III Colon Cancer Post-Adjuvant
ctDNA positivity after completing standard adjuvant chemo triggers second-line chemotherapy. Addresses what to do when ctDNA-MRD persists — the question after the first question.
Notable concepts
Smaller in enrollment but each testing a distinct clinical question — de-escalation, early relapse, pan-tumor, and surgery timing.
Elacestrant in ER+ Breast Cancer With ctDNA Relapse (EORTC)
ctDNA rise — before any imaging finding — triggers elacestrant vs. standard endocrine therapy. First pivotal trial treating molecular relapse as clinical relapse. 109 European sites.
Active Surveillance vs. Definitive Therapy in Bladder Cancer
ctDNA-negative complete responders skip definitive local therapy and enter active surveillance. De-escalation trials are rare and harder to design — this one asks whether the blood test can replace surgery.
ctDNA-Adaptive Immuno-Chemotherapy in Lung Cancer
ctDNA response after cycle 1 of pembrolizumab determines whether patients continue immuno-chemo or escalate. Real-time treatment adaptation at the earliest measurable timepoint.
Tislelizumab in Pan-Tumor Molecular Residual Disease (Gustave Roussy)
ctDNA-defined MRD triggers tislelizumab immunotherapy across four solid tumor types. Pan-tumor ctDNA trials are the furthest-reaching application — one assay, one decision rule, multiple cancer markets.
LIQUIPANC: ctDNA Stratifies Surgery vs. Chemo in Pancreatic Cancer
ctDNA-positive patients receive neoadjuvant chemotherapy first; ctDNA-negative go straight to surgery. A blood test replaces surgical judgment for the highest-stakes timing decision in GI oncology.
The harder question
Most Phase 3 ctDNA trials ask “should we give more treatment?” Only two ask the inverse: can ctDNA-negativity justify giving less? De-escalation trials are scientifically harder to design — a negative ctDNA result must be shown to be safe as a reason to skip treatment, not just prognostically reassuring. But de-escalation is where the commercial value is largest: sparing patients from unnecessary chemotherapy has quality-of-life implications, cost implications, and a compelling payer rationale. The de-escalation pipeline is underbuilt relative to its opportunity.
Methodology: Phase counts reflect recruiting trials listing “ctDNA” as an intervention, filtered by phase using Essie expression syntax (filter.advanced=AREA[Phase]PHASEx); the Phase 2 total shown is an approximate count. Cancer-type Phase 3 counts combine the ctDNA intervention filter with a condition search. The decision-type breakdown is a manual classification of the ~25 Phase 3 trials we track (and a Phase 2 sample), based on registry entries — point-in-time, while the phase counts above refresh live. Some trials span multiple cancer types and are classified by primary condition. Data refreshes daily. Last updated: June 17, 2026.