Table 1

Completed clinical trials

Target		Drug	Trial number	Cancer type	ORR and control rate	Treatment-related adverse events (%, if available)
OX40	Monotherapy	9B12	NCT01644968	Solid tumors (melanoma, gastrointestinal, renal cell, prostate, etc)	No CR or PR 40% with SD	Lymphopenia, fatigue, rash, pruritus, fever, chills
	Monotherapy	MEDI0562	NCT02318394	Solid tumors (head and neck, bladder)	4% with PR	Fatigue, infusion-related reaction, fever
	Combination therapy	MOXR0916 given with atezolizumab	NCT02410512	Solid tumors	4% with PR	Mostly grade 3, one related grade 3 of pneumonitis
4-1BB	Monotherapy	Urelumab (BMS-663513)	NCT00309023 until 2008. NCT01471210 thereafter	Solid tumors (renal cell, ovarian, etc) Solid tumors (melanoma, renal cell, ovarian) and non-Hodgkin's lymphoma	No CR or PR, 2.6% with SD N/A	Grade 3–4 neutropenia (5%), fatigue (all grade) (26%), grade 3–4 transaminitis (11%), two hepatotoxicity-related deaths in each trial
	Monotherapy	Utomilumab (PF-05082566)	NCT01307267	Solid tumors (Meckel cell carcinoma, and colon, gastric, and pancreatic cancers)	5.3% with ORR 24.5% with SD	Fatigue, fever, decreased appetite, dizziness, and rash (<10% of patients)
	Combination therapy	Utomilumab plus pembrolizumab	NCT02179918	Solid tumors (non-small cell lung, renal cell, and head and neck cancers)	26.1% with PR or CR	Fatigue (34.8%), rash, decreased appetite (13%), nausea
	Combination therapy	Urelumab plus nivolumab	NCT02253992	Advanced solid tumor including melanoma, non-small cell lung cancer, and diffuse larger B cell lymphoma	50% in evaluable melanoma patients. 3% in other cohorts	Fatigue (31%), ALT increase (11%), anemia (10%) and AST increase (9%)
GITR	Monotherapy	TRX-518	NCT01239134	Solid tumors (melanoma, non- small cell lung and colorectal cancers)	14% with irSD	Cough and fatigue (28% each); vomiting, abdominal pain, and nausea (18% each); dyspnea and anorexia (15% each)
		AMG228	NCT02437916	Solid tumors (colorectal, head and neck, urothelial and non-small cell lung cancer)	No CR or PR; 23%with irSD	Fatigue (13%), infusion-related reaction (7%), fever (7%), decreased appetite (7%), and hypophosphatemia (7%)
		MEDI1873	NCT02583165	non-small cell lung cancer, head and neck squamous cell carcinoma, colorectal cancer	42.5% with SD	Headache (25%) and infusion- related reaction, Grade three nausea/vomiting, and ST elevation myocardial infarction
	Monotherapy and combination therapy	MK-4166 with or without pembrolizumab	NCT02132754	Solid tumors and melanoma expansion cohorts	9% for the combination therapy groups. 69% with ICI-naïve melanoma patients in the expansion	Fatigue, infusion-related reaction, nausea, abdominal pain, and pruritus, DLT of bladder perforation
CD40	Monotherapy	rhuCD40L		Solid tumors and non-Hodgkin's lymphoma	6% with PR, 38% with SD	Transient elevations of serum liver transaminases
	Monotherapy	CP-870,893	NCT02225002	Solid tumors (melanoma, non-small cell lung cancer, sarcoma, cholangiocarcinoma)	14% of all patients and 27% of melanoma patients with PR	CRS, transient hematologica; abnormalities, LFT abnormalities
	Combination therapy	CP-870,893 plus gemcitabine		Pancreatic cancer	19% with PR, 52% with SD	CRS, fatigue, nausea, vomiting, hematologic events
		CP-870 to 893 plus paclitaxel and carboplatin	NCT00607048	Solid tumors (mostly melanoma, renal cell carcinoma, sarcoma)	20% with PR; in 30 evaluable patients, 40% with SD	Fatigue (81%), neuropathy (46%), Cytokine release syndrome (42%), alopecia (42%), constipation (38%), nausea (37%), neutropenia (38%), 1 DLT of Cardiovascular syndrome
		CP-870,893 plus pemetrexed and cisplatin	*ACTRN12609000294257	Mesothelioma	40% with PR	CRS (80%), hematological adverse events (consistent with reported chemotherapy toxicities), Grade four splenic infarction, and 1 grade 3 confusion and hyponatremia.

*Conducted in Australia and New Zealand.
ALT, alanine aminotransferase; AST, aspartate transaminase; CR, complete response; CRS, cytokine release syndrome; DLT, dose-limiting toxicity; ICI, immune checkpoint inhibitor; irSD, immune-related stable disease; LFT, liver function test; N/A, not applicable; ORR, overall response rate; PR, partial response; SD, stable disease.