# ctDNA-triggered escalation in early TNBC

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

## TL;DR

Instead of treating everyone after surgery, test blood every few months and treat only when tumour DNA reappears.

## Summary

Instead of treating every early TNBC patient after surgery, this idea tests blood every few months and escalates only when tumour DNA reappears. MRD-positive patients would be randomised to immediate ADC plus immunotherapy versus surveillance, while MRD-negative patients could omit adjuvant pembrolizumab. IMvigor011 proved the concept in bladder cancer, TNBC relapses early and sheds ctDNA, and the ZEST trial failed on feasibility rather than concept. The test is a platform trial in post-KEYNOTE-522 patients with serial Signatera-type testing, arms of Dato-DXd, sacituzumab govitecan or sac-TMT and a DFS endpoint. At early-clinical maturity it addresses the bottleneck Dormant cells and minimal residual disease.

## Fields

- Kind: Idea
- Last checked: 2026-09-04
- Hypothesis: MRD-positive TNBC patients randomised to immediate ADC + IO have superior DFS versus surveillance, and MRD-negative patients can safely omit adjuvant pembrolizumab.
- Rationale: Lead time of 6-12 months over imaging; treating microscopic disease with ADCs may be curative where treating macroscopic relapse is not.
- Proposed test: Platform trial enrolling post-KEYNOTE-522 patients with serial Signatera-type testing; randomise MRD+ to intervention arms (Dato-DXd, sacituzumab, sac-TMT) vs observation; primary endpoint DFS; embed a de-escalation arm for MRD-negative pCR patients.
- Maturity: early-clinical

## Sources

- ClinicalTrials.gov NCT04660344: IMvigor011: https://clinicaltrials.gov/study/NCT04660344
- ClinicalTrials.gov NCT05812807: OptimICE-pCR (A012103): https://clinicaltrials.gov/study/NCT05812807

## Connected records

- pairings: [ctDNA MRD → adjuvant therapy decision](https://onco.cc/pairings/ctdna-mrd-to-adjuvant/)
- cancers: [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Signatera](https://onco.cc/drugs/signatera/)
- terms: [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- trials: [IMvigor011](https://onco.cc/trials/imvigor011/), [OptimICE-pCR (A012103)](https://onco.cc/trials/optimice-pcr/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- ideas: [A national residual-disease weather service: serial blood tests for every curatively treated patient, pooled](https://onco.cc/ideas/idea-moon-mrd-weather-service/), [A ring-fenced metastasis programme with metastasis-specific endpoints](https://onco.cc/ideas/idea-fund-metastasis-moonshot/)
- key papers: [KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer](https://onco.cc/key-papers/paper-keynote-522-nejm-2022/)

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