# Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials

Source: https://onco.cc/ideas/idea-tr2-ctdna-mrd-qualification/  
OnCo record `idea-tr2-ctdna-mrd-qualification` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

If a blood test reliably shows whether cancer will come back after surgery, trials could use it instead of waiting years for relapse. Regulators have a process to bless such a test; oncology should use it.

## Summary

FDA's Biomarker Qualification Program creates a drug-independent, context-of-use qualification for biomarkers. ctDNA clearance after adjuvant therapy correlates strongly with recurrence in colorectal, bladder and lung cancer, and trial-level meta-analysis is becoming possible as ctDNA-guided trials report. A consortium submission to qualify ctDNA clearance as a reasonably likely surrogate for disease-free survival in defined settings would let adjuvant trials read out in one to two years rather than five.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Trial-level correlation between ctDNA clearance rate and disease-free survival hazard ratio across adjuvant trials will be strong enough (R squared above 0.7) to support qualification in at least one tumour type by 2029.
- Rationale: Pathological complete response and MRD in haematological cancers have been accepted for accelerated approval on similar reasoning; ctDNA has cleaner biology and is measured uniformly.
- Proposed test: Pool patient- and trial-level data from completed ctDNA-guided adjuvant trials (DYNAMIC, CIRCULATE, IMvigor011 and others) and run the surrogate validation analyses required for qualification.
- Maturity: early-clinical
- Actor: regulator

## Sources

- FDA Biomarker Qualification Program: https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program

## Connected records

- ideas: [ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer](https://onco.cc/ideas/idea-ctdna-guided-adjuvant-crc/)
- pairings: [ctDNA MRD → adjuvant therapy decision](https://onco.cc/pairings/ctdna-mrd-to-adjuvant/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Signatera](https://onco.cc/drugs/signatera/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- trials: [CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)](https://onco.cc/trials/circulate-japan/), [DYNAMIC](https://onco.cc/trials/dynamic/), [IMvigor011](https://onco.cc/trials/imvigor011/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- key papers: [GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold](https://onco.cc/key-papers/paper-galaxy-signatera-nat-med-2023/)
- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/), [Diagnostics roadmap: stains → gene panels → blood tests that decide treatment](https://onco.cc/roadmaps/diagnostics-roadmap/), [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/)
- cancers: [Resectable stage I to III non-small-cell lung cancer](https://onco.cc/cancers/resectable-nsclc/)

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