Table 3. Examples of ongoing adaptive trials using ctDNA kinetics to modify treatment regimens.

Trial	Population	Initial therapy	Adaptation
NCT04093167	Metastatic NSCLC	Immune checkpoint inhibitor (pembrolizumab)	ctDNA after 1 to 3 cycles determines whether patients continue or switch to next standard line of therapy
NCT04166487	Metastatic NSCLC	Immune checkpoint inhibitor (pembrolizumab)	Cycle 2 ctDNA determines candidates for addition of chemotherapy
NCT04358562	EGFR mutant NSCLC	Targeted therapy (gefitinib)	Lack of ctDNA clearance at 8 weeks prompts addition of second targeted agent (anlotinib)
NCT04680260 (OPTIMISE)	Oligometastatic CRC	Radical-intent resection or ablative therapy	Randomization to standard of care or ctDNA-guided intensified adjuvant chemotherapy regimen
NCT04567420 (DARE)	High-risk stage II-III estrogen receptor–positive breast cancer	Adjuvant hormone therapy (letrozole or tamoxifen)	Increase in ctDNA prompts switch to combination hormone therapy and targeted agent (fulvestrant and palbociclib)
NCT03808441 (CACTUS)	BRAF mutant melanoma	Targeted therapy (dabrafenib + trametinib)	ctDNA decrease prompts switch to immunotherapy (nivolumab + ipilimumab)