OnCo
ideasIdea

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

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.

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.

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.
What would test it
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
Who has to act
regulator
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks

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