Table 2

ctDNA-guided interventional ICI clinical trials

Trial (NCT ID)	Target enrollment	Indication	Treatment	ctDNA platform	Primary endpoint	Setting and references
NCT04966663	66	Resected localized NSCLC	Adjuvant chemotherapy+nivolumab	Inivata RaDaR	DFS	T1-2N0M0 or T3/T4 multifocal tumors that are MRD+at 3–6 weeks post complete surgical resection are eligible
NCT04385368 (MERMAID-1)	332	Resected stage II-III NSCLC	Adjuvant chemotherapy+durvalumab vs SOC chemotherapy	ArcherDX	DFS in MRD+pts	Stratified by MRD status at 3–4 weeks postsurgery(147)
NCT04642469 (MERMAID-2)	284	Resected stage II-III NSCLC	Adjuvant chemotherapy as per SOC then durvalumab vs placebo	ArcherDX	DFS in PD-L1+pts	Pts who are MRD+within 96 weeks surveillance period after curative-intent therapy are randomized(148)
NCT04849364 (PERSEVERE)	197	Residual TNBC after pre-operative therapy	Atezolizumab+chemotherapy/PARP/PI3K combinations	Not reported	2 year DFS	ctDNA-directed umbrella study for pts with detectable ctDNA postoperative
NCT04138628 (TOMBOLA)	282	Resected urothelial carcinoma (radical cystectomy)	Atezolizumab	Not reported	% of patients with molecular and radiographic CR	Pts with detectable ctDNA postoperative are eligible
NCT04093167	50	Treatment-naïve, advanced PD-L1+NSCLC	Pembrolizumab	PGDx	Concordance between molecular response and radiologic response	Molecular response after 1–3 cycles determines whether chemotherapy is added.
NCT04166487	40	Treatment-naïve, advanced NSCLC	Pembrolizumab	Inivata InVision	6 month PFS	Chemotherapy added based on ctDNA response after two cycles.
NCT03178552 (BFAST)	440	Treatment-naïve, advanced NSCLC	Atezolizumab versus SOC chemotherapy	Foundation ACT	PFS	ctDNA-directed umbrella study with arm for blood TMB+pts68 149
NCT04585490	48	Unresectable stage III NSCLC	Consolidative durvalumab+chemotherapy	AVENIO	Change in ctDNA level following consolidative chemotherapy	Pts with detectable ctDNA after chemoRT have chemotherapy added to SOC durvalumab
NCT03808441 (CAcTUS)	40	Advanced BRAF V600E/K/R melanoma	Nivolumab+ipilimumab	Not reported	% of patients meeting 80% ctDNA threshold	Pts are switched from BRAF targeted therapy to immunotherapy when BRAF ctDNA level is ≤80% from baseline(150)
NCT04966676 (ATLAS)	50	Metastatic NSCLC	Nivolumab+ipilimumab	Guardant	6 month PFS	Patients with increasing or stable ctDNA given platinum-doublet chemotherapy

BFAST, Blood First Assay Screening Trial; chemoRT, chemoradiation; CR, complete response; ctDNA, cell-free tumor DNA; DFS, disease-free survival; ICI, immune checkpoint inhibitor; MRD, minimal residual disease; PFS, progression-free survival; SOC, standard of care; TMB, tumor mutational burden.