Immune Checkpoint Modulation in Colorectal Cancer: What’s New and What to Expect

Table 1

Clinical trials testing immune checkpoint modulators in colorectal cancer (according to https://www.clinicaltrial.gov/, 19th of June 2015).

Target	Compound	NCT tracker	Phase	Tumor type	Status	Combination (target)
Antagonistic monoclonal antibodies
PD-1	AMP-224; <Amplimmune	NCT01352884	I	Advanced solid tumors or CTCL	Completed
		NCT02298946	I	mCRC	Recruiting	+ Stereotactic body RT; + Cyclophosphamide
	PDR001; <Novartis	NCT02404441	I; II	Advanced malignancies; incl. only PD-L1^+ MSI-H CRC	Recruiting
	Nivolumab; BMS-936558; MDX-2206; ONO-4538; <Bristol-Myers Squibb	NCT01629758	I	Locally advanced or metastatic solid tumors	Completed	+ Denenicokin (IL-21)
		NCT02060188	II	Recurrent and mCRC: MSI-H and MSI-L	Recruiting	+ Ipilimumab (CTLA-4)
		NCT02408861	I	HIV-associated solid tumors	Not yet recruiting	+ Ipilimumab (CTLA-4)
		NCT00836888	I	Advanced malignant solid tumors in Japan	Not yet recruiting
		NCT01714739	I	Advanced solid tumors	Recruiting	+ Lirilumab (KIR)
	Pembrolizumab; MK-3475; <Merck	NCT02054806	I	Biomarker-positive solid tumors	Recruiting
		NCT02179918	I	Advanced solid tumors	Recruiting	+ PF-05082566 (CD137)
		NCT02332668	I/II	Advanced Melanoma; advanced relapsed PD-L1^+ malignancies	Recruiting
		NCT01876511	II	MSI-H (non)-CRC	Recruiting
		NCT02460198	II	Previously treated locally advanced unresectable/MSI-H mCRC	Not yet recruiting
	REGN2810; <Regeneron	NCT02383212	I	Advanced malignancies	Recruiting	+ Hypofractionated RT; + Cyclophosphamide
	BGB-A317; <BeiGene	NCT02407990	I	Advanced cancers	Recruiting
	MEDI0680; AMP-514; <AstraZeneca	NCT02013804	I	Advanced cancers	Recruiting
		NCT02118337	I	Advanced cancers	Recruiting	+ MEDI4736; (PD-L1)
PD-L1	MEDI4736; <AstraZeneca	NCT01693562	I/II	Solid tumors	Recruiting
		NCT02227667	II	Advanced CRC	Recruiting
	MDX-1105; BMS-936559; <Bristol-Myers Squibb	NCT00729664	I	Relapsed/refractory solid tumors (incl. CRC)	Active, not recruiting
	Avelumab; MSB0010718C; <MerckKGaA and Pfizer	NCT01943461	I	Metastatic/locally advanced solid tumors	Recruiting
		NCT01772004	I	Solid tumors	Recruiting
	MPD-L3280A; MSB0010718C; <Roche	NCT01375842	I	Locally advanced/metastatic solid tumors incl. CRC	Recruiting
		NCT01633970	I	Locally advanced or metastatic solid tumors (incl. >10 patients with CRC)	Recruiting	+ Avastin (VEGF); + Chemotherapy
		NCT02350673	I	Metastatic/locally advanced solid tumors	Not yet recruiting	+ RO6895882 (IL-2)
		NCT01988896	I	Metastatic/locally advanced solid tumors incl. KRAS-mutant mCRC	Not Yet recruiting	+ Cobimetinib (MEK)
CTLA-4	Ipilimumab; MDX-010; YERVOY; <Bristol-Myers Squibb	NCT01750983	I	Advanced or metastatic cancer	Recruiting	+ Lenalidomide
		NCT02239900	I/II	Advanced solid tumors with spread to liver, lung, or adrenal gland	Recruiting	+ Stereotactic body radiation
	Tremelimumab; Ticilimumab; CP-675,206; <Pfizer	NCT00313794	II	mCRC	Completed
		NCT01975831	I	Advanced solid tumors (incl. CRC)	Recruiting	+ MEDI4736 (PD-L1)
		NCT02261220	I	Advanced solid tumors	Recruiting	+ MEDI4736; (PD-L1)
LAG-3	BMS-986016; <Bristol-Meyers Squibb	NCT01968109	I	Solid tumors	Recruiting	+ Nivolumab (PD-1)
	LAG-525; <Novartis	NCT02460224	I; II	Advanced solid tumors (incl. PD-L1^+CRC MSI-H)	Not yet recruiting	+ PDR001 (PD-1)
CD70	ARGX-110; <arGEN-x	NCT01813539	ɪ	Refractory or relapsing CD70^+ malignancies	Recruiting
Agonistic monoclonal antibodies
CD27	Varlilumab; CDX-1127; <Celldex	NCT01460134	I	Solid tumors (incl. CRC)	Recruiting
		NCT02335918	I/II	Advanced refractory solid tumors (incl. CRC)	Recruiting	+ Nivolumab (PD-1)
CD134; (OX40)	MEDI6469; <AgonOx	NCT02318394	I	Recurrent or metastatic solid tumors	Recruiting
		NCT02205333	I/II	Advanced solid tumors/aggressive B-cell lymphomas	Recruiting	+ Tremelimumab (CTLA-4); + MEDI4736 (PD-L1); + Rituximab
	MEDI6383; <AgonOx	NCT02221960	I	Advanced solid tumors	Recruiting
	MOXR0916; RG7888; <Genentech Inc.	NCT02219724	I	Metastatic/locally advanced solid tumors	Recruiting
		NCT02410512	I	Locally advanced, recurrent, or metastatic incurable solid tumors	Recruiting	+ MPL3280A (PD-L1)
Agonistic monoclonal antibodies
GITR	TRX518; <Tolerx	NCT01239134	I	Solid tumors/malignant melanoma	Recruiting
	MK-4166; <Merck	NCT02132754	I	Solid tumors	Recruiting	+ Pembrolizumab (PD-1)
CD137; (4-1BB)	Urelumab; BMS-663513; <Bristol-Meyers Squibb	NCT01471210	I	Advanced solid tumors/B-cell NHL	Recruiting
		NCT02110082	I	CRC/head and neck cancer	Recruiting	+ Cetuximab (EGFR)
		NCT02253992	I/II	Advanced solid tumor/advanced B-cell NHL	Recruiting	+ Nivolumab (PD-1)
	PF-05082566; <Pfizer	NCT02444793	I/II	Advanced/metastatic solid tumors	Recruiting	+ Mogamulizumab (CCR4)
CD40	CP-870,893; <Pfizer	NCT02225002	I	Advanced solid tumors	Completed
		NCT00607048	I	Metastatic solid tumors	Completed	+ Paclitaxel/Carboplatin
	RO7009789; <Roche	NCT02304393	I	Metastatic/locally advanced solid tumors	Recruiting	+ MPD-L3280A (PD-L1)
	ADC-1013; <AlligatorBioscience	NCT02379741	I	Advanced solid tumors	Recruiting
	ChiLob 7/4; <Southampton, UK	NCT01561911	I	CD40^+ solid tumors/refractory DLBCL	Completed
	SEA-CD40; <Seattle genetics	NCT02376699	I	Advanced metastatic tumors/unresectable solid malignancies	Recruiting

PD-1, programmed death-1; PD-L1, programmed death ligand-1; CTLA-4, cytotoxic T lymphocyte antigen-4; CD, cluster of differentiation; LAG-3, lymphocyte activation gene-3; GITR, glucocorticoid-induced tumor necrosis factor receptor-related protein; CTCL, cutaneous T cell lymphoma; CRC, colorectal cancer; mCRC, metastatic CRC; MSI, microsatellite instability; MSI-H, MSI-high; MSI-L, MSI-low; HIV, human immunodeficiency virus; KRAS, Kirsten rat sarcoma viral oncogene; NHL, non-Hodgkin lymphoma; DLBL, diffuse large B cell lymphoma; IL, interleukin; KIR, killer-cell immunoglobulin-like receptor; RT, radiotherapy; VEGF, vascular endothelial growth factor; MEK, mitogen-activated protein kinase kinase; EGFR, epidermal growth factor receptor; CCR4, C-C chemokine receptor type 4.