Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond

Table 4 Agents targeting immune checkpoints under clinical investigation for the treatment of drug-resistant and metastatic colorectal cancer

Agent	Targeted molecule	Condition	Study phase	Clinical trial identifier
Camrelizumab	PD-1	Non-MSI-H/dMMR mCRC	Phase II	NCT04866862
		mCRC	Phase II	NCT03912857
Tislelizumab	PD-1	HER2-Positive Advanced CRC	Phase II	NCT05493683
Nivolumab	PD-1	Later-lines treatment of mCRC	Phase III	NCT05328908
		Advanced CRC	Phase I	NCT02991196
		Metastatic MSS CRC	Phase I	NCT03993626
		mCRC	Phase II	NCT04166383
Pembrolizumab (MK-3475)	PD-1	MSI-H/dMMR CRC	Phase III	NCT05239741
		mCRC	Phase III	NCT04776148
		MMR-proficient mCRC	Phase II	NCT03519412
		HER2-expressing mCRC	Phase II	NCT03631407
		HER2-expressing mCRC	Phase II	NCT05333809
PDR-001	PD-1/PD-L1	mCRC	Phase I	NCT03081494
		First-line mCRC	Phase I	NCT03176264
Toripalimab	PD-1/PD-L1	mCRC	Phase II	NCT03927898
Avelumab	PD-1/PD-L1	mCRC	Phase II	NCT03150706
		mCRC	Phase II	NCT03258398
Atezolizumab	PD-L1	mCRC	Phase III	NCT05425940
		mCRC	Phase III	NCT02788279
		First-line mCRC	Phase II	NCT02291289
		Refractory CRC	Phase II	NCT02873195
Relatlimab	LAG-3	Later-lines treatment of mCRC	Phase III	NCT05328908
Tremelimumab	CTLA-4	mCRC	Phase I/II	NCT03202758
		mCRC	Phase II	NCT03122509
		mCRC	Phase II	NCT03428126
		mCRC	Phase II	NCT03435107

PD-1: Programmed death-1; PD-L1: Programmed death ligand-1; mCRC: metastatic colorectal cancer; MSI-H/dMMR: Microsatellite instability-high/mismatch repair deficient; MSS: Microsatellite stable; HER2: Human epidermal growth factor receptor 2; LAG-3: Lymphocyte activation gene 3; CTLA-4: Cytotoxic T lymphocyte-associated antigen 4.