Table 4.

Ongoing trials retrospectively assessing the role of liquid biopsy in mCRC

Study and phase of research	Study population	Liquid biopsy analysis	Intervention	Primary endpoint	Role of liquid biopsy analysis
CAVE (NCT04561336) Phase II	Pretreated RAS WT mCRC	ctDNA	Combination of avelumab plus cetuximab	OS	To compare OS and PFS in ctDNA RAS/BRAF WT and MT populations
CR-SEQUENCE (NCT03635021) Phase III	Untreated RAS WT left-sided mCRC	ctDNA	FOLFOX plus panitumumab followed by FOLFIRI plus bevacizumab vs FOLFOX plus bevacizumab followed by FOLFIRI plus panitumumab	PFS	To state the clinical impact of clonal dynamics of ctDNA
KISIMA-01 (NCT04046445) Phase Ib	Pretreated mCRC progressed to standard-of-care therapies	ctDNA	ATP128, with or without BI 754091	Safety and tolerability of ATB128 and BI754091	To detect early signal of relapse through ctDNA in patients treated with ATP128 and BI 754091 before and after liver surgery
IMPROVE (NCT04425239) Phase II	Untreated RAS/BRAF WT mCRC	ctDNA	Continuous vs intermittent panitumumab and FOLFIRI in first line	PFS	To evaluate potential biomarkers of primary and secondary resistance analyzing ctDNA
iRE-C (NCT04108481) Phase I–II	Liver predominant mCRC	ctDNA	Yttrium-90 radioembolization (Y90-RE) in combination with durvalumab	Safety and tolerability of Yttrium-90 radioembolization combined with durvalumab and ORR	To determine changes in the expression profile and in ctDNA levels after treatment
NCT04169347 Phase II	Left-sided RAS WT mCRC	ctDNA	FOLFOXIRI plus panitumumab	ORR	To evaluate velocity of response through ctDNA clearance
NCT03829410 Phase I–II	RAS MT mCRC	ctDNA	Onvansertib in combination with FOLFIRI and bevacizumab	Safety and tolerability of onvansertib plus FOLFIRI plus bevacizumab and ORR	To evaluate reduction of RAS MT in ctDNA
AIO–KRK-01160 (NCT04034459) Phase II	BRAF MT mCRC	Not specified	FOLFOXIRI plus bevacizumab vs FOLFOXIRI plus cetuximab in first line	ORR	To investigate molecular biomarkers for the prediction of sensitivity and secondary resistance of cetuximab
NCT04247256 Phase I–II	FOLFIRI-resistant mCRC	ctDNA	Combination of SCO-101 with FOLFIRI rechallenge	Safety and tolerability of SCO-101 and ORR	To evaluate the change in ctDNA from baseline until first computed tomography scan

ctDNA circulating tumor DNA, mCRC metastatic colorectal cancer, MT mutated, ORR overall response rate, OS overall survival, PFS progression-free survival, WT wild-type