When should you collect ctDNA in your clinical trials to best predict survival?

A new study from Friends of Cancer Research analyzed 918 NSCLC patients to answer this.

Two Windows, Different Stories...

Researchers compared early (T1: 0-7 weeks) versus late (T2: 7-13 weeks) collection timepoints using three molecular response cutoffs: ≥50%, ≥90%, and 100% reduction of ctDNA from baseline.

All three cutoffs showed significant associations with survival at both timepoints.

But timing mattered differently by treatment modality.

👉 Anti-PD(L)1 patients: Strong associations at both T1 and T2
👉 Chemotherapy patients: Weak associations at T1, became significant at T2

This reflects different ctDNA kinetics by mechanism of action.

Statistically, T2 had marginally stronger survival associations overall.
But T1 also offers something critical: earlier signal—often at or before first radiographic scan.

**What This Means for Your Trials**
👉 Early ctDNA collections windows can be complementary to RECIST criteria, especially where RECIST shows stable disease. This can be used in support of your dose decisions, and also to support the story of your drug early on.
👉 Specific collection times may be more optimal for association with overall survival
👉 The optimal timepoint may be unique to the treatment modality of your drug
👉 ctDNA data may come in earlier than first radiographic scan (although in practice I've found that, because of the longer turnaround time for ctDNA results usually come in later even if the collection was a few weeks before the scan).

This study provides a great framework you can apply to your Phase 1 prospectively to provide evidence that clearance of ctDNA at a specific timepoint is associated with overall survival and therefore could be useful for proving the drug's utility in later phases.