OnCo
ideasIdea

ctDNA-triggered escalation in early TNBC

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

IMvigor011 proved the concept in bladder cancer. TNBC relapses early and sheds ctDNA, making it the ideal breast subtype for MRD-guided therapy. The ZEST trial (niraparib) failed on feasibility, not concept.

Confidence
30%55%likelyOnCo editors (initial estimate), 2026-09-07 · IMvigor011 proved the concept in bladder; TNBC shedding and feasibility are the risks (ZEST).
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.
What would test it
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

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