ideasIdea
Kill combination arms early using circulating tumour DNA, before waiting for scans
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.
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.
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.
What would test it
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
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
3
Bottlenecks it attacks
- Too many combinations to test · There are thousands of possible drug pairs and sequences. Trials can test a few dozen a year.
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.