# Kill combination arms early using circulating tumour DNA, before waiting for scans

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

## TL;DR

A blood test at six weeks can show whether a treatment is doing anything. Trials should use it to drop failing combinations fast and move patients on.

## Summary

Molecular response (ctDNA clearance or fall below a threshold at 6 to 9 weeks) correlates with progression-free and overall survival across several tumour types and drug classes. Platform trials could use pre-specified ctDNA futility rules at 20 patients per arm to stop non-performing combinations months earlier than radiological endpoints allow.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Arms stopped for ctDNA futility would, had they continued, have failed their radiological primary endpoint in at least 85% of cases; adopting the rule increases the number of arms tested per year by at least 50%.
- Rationale: Several studies show early ctDNA dynamics predict RECIST response and survival on immunotherapy and targeted therapy. Futility, unlike efficacy, needs only a reliable negative predictor.
- Proposed test: Run the rule in shadow mode in an existing platform for two years, recording what would have been stopped and comparing with final radiological results.
- Maturity: early-clinical
- Actor: research

## Sources

- Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017): https://doi.org/10.1016/j.cell.2017.11.009

## Connected records

- companies: [Guardant Health](https://onco.cc/companies/guardant-health/), [Natera](https://onco.cc/companies/natera/)
- ideas: [CD8 PET to stop or switch immunotherapy early](https://onco.cc/ideas/idea-cd8-pet-io/), [Let the trial learn: response-adaptive allocation across many combination arms](https://onco.cc/ideas/idea-tr2-bandit-allocation/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/), [RECIST](https://onco.cc/terms/recist/)
- bottlenecks: [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- key papers: [Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy](https://onco.cc/key-papers/paper-palmer-cell/)

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