Table 2

ctDNA-guided interventional ICI clinical trials

Trial (NCT ID)Target enrollmentIndicationTreatmentctDNA platformPrimary endpointSetting and references
NCT0496666366Resected localized NSCLCAdjuvant chemotherapy+nivolumabInivata RaDaRDFST1-2N0M0 or T3/T4 multifocal tumors that are MRD+at 3–6 weeks post complete surgical resection are eligible
NCT04385368 (MERMAID-1)332Resected stage II-III NSCLCAdjuvant chemotherapy+durvalumab vs SOC chemotherapyArcherDXDFS in MRD+ptsStratified by MRD status at 3–4 weeks postsurgery(147)
NCT04642469 (MERMAID-2)284Resected stage II-III NSCLCAdjuvant chemotherapy as per SOC then durvalumab vs placeboArcherDXDFS in PD-L1+ptsPts who are MRD+within 96 weeks surveillance period after curative-intent therapy are randomized(148)
NCT04849364 (PERSEVERE)197Residual TNBC after pre-operative therapyAtezolizumab+chemotherapy/PARP/PI3K combinationsNot reported2 year DFSctDNA-directed umbrella study for pts with detectable ctDNA postoperative
282Resected urothelial carcinoma (radical cystectomy)AtezolizumabNot reported% of patients with molecular and radiographic CRPts with detectable ctDNA postoperative are eligible
NCT0409316750Treatment-naïve, advanced PD-L1+NSCLCPembrolizumabPGDxConcordance between molecular response and radiologic responseMolecular response after 1–3 cycles determines whether chemotherapy is added.
NCT0416648740Treatment-naïve, advanced NSCLCPembrolizumabInivata InVision6 month PFSChemotherapy added based on ctDNA response after two cycles.
NCT03178552 (BFAST)440Treatment-naïve, advanced NSCLCAtezolizumab versus SOC chemotherapyFoundation ACTPFSctDNA-directed umbrella study with arm for blood TMB+pts68 149
NCT0458549048Unresectable stage III NSCLCConsolidative durvalumab+chemotherapyAVENIOChange in ctDNA level following consolidative chemotherapyPts with detectable ctDNA after chemoRT have chemotherapy added to SOC durvalumab
NCT03808441 (CAcTUS)40Advanced BRAF V600E/K/R melanomaNivolumab+ipilimumabNot reported% of patients meeting 80% ctDNA thresholdPts are switched from BRAF targeted therapy to immunotherapy when BRAF ctDNA level is ≤80% from baseline(150)
50Metastatic NSCLCNivolumab+ipilimumabGuardant6 month PFSPatients 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.