Table 2.

IO-based randomized trials using ctDNA MRD for patient selection, treatment decisions, or as an early endpoint

Trial and disease	Study arms	Primary endpoint(s)	Use of ctDNA
c-TRAK TN NCT03145961 Moderate or high-risk early-stage TNBC	Adjuvant pembrolizumab versus observation	ctDNA by 12 months; ctDNA by 24 months; absence of ctDNA/ DFS at 6 months	Assign treatment: ctDNA-positive within 12 months randomized to pembrolizumab or observation; ctDNA-negative observed
MERMAID-1 NCT04385368 NSCLC stage II, III	Adjuvant durvalumab+SOC chemotherapy versus placebo+SOC chemotherapy	DFS	Inclusion criteria: ctDNA-positive after surgery
MERMAID-2 NCT04642469 NSCLC stage II, III	Adjuvant durvalumab versus placebo	DFS	Inclusion criteria: ctDNA-positive during 96-week surveillance period
IMvigor011 NCT04660344 Muscle-invasive bladder cancer	Adjuvant Atezolizumab versus chemotherapy	DFS	Inclusion criteria: ctDNA-positive within 20 weeks after cystectomy
DETECTION NCT04901988 Melanoma stage IIB/C	Adjuvant nivolumab versus observation	OS	Assign treatment: ctDNA-positive treated with nivolumab
SCION NCT04944173 NSCLC stage I	Durvalumab+SABR (ctDNA-negative) versus durvalumab+SABR (ctDNA-positive) versus Durvalumab+SABR followed by eight additional cycles of Durvalumab (ctDNA-positive)	DFS	Assign treatment: ctDNA-positive randomized to either no further therapy or eight additional cycles of durvalumab

ctDNA, circulating tumor DNA; DFS, disease-free survival; IO, immuno-oncology; MRD, molecular residual disease; NSCLC, non-small cell lung cancer; SABR, stereotactic ablative radiotherapy; SOC, standard of care; TNBC, triple negative breast cancer.