Table 1

Completed clinical trials

TargetDrugTrial numberCancer typeORR and control rateTreatment-related adverse events (%, if available)
OX40Monotherapy9B12NCT01644968Solid tumors (melanoma, gastrointestinal, renal cell, prostate, etc)No CR or PR
40% with SD
Lymphopenia, fatigue, rash, pruritus, fever, chills
MEDI0562NCT02318394Solid tumors (head and neck, bladder)4% with PRFatigue, infusion-related reaction, fever
Combination therapyMOXR0916 given with atezolizumabNCT02410512Solid tumors4% with PRMostly grade 3, one related grade 3 of pneumonitis
4-1BBMonotherapyUrelumab (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
Grade 3–4 neutropenia (5%), fatigue (all grade) (26%), grade 3–4 transaminitis (11%),
two hepatotoxicity-related deaths in each trial
Utomilumab (PF-05082566)NCT01307267Solid 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 therapyUtomilumab plus pembrolizumabNCT02179918Solid tumors (non-small cell lung, renal cell, and head and neck cancers)26.1% with PR or CRFatigue (34.8%), rash, decreased appetite (13%), nausea
Urelumab plus nivolumabNCT02253992Advanced solid tumor including melanoma, non-small cell lung cancer, and diffuse larger B cell lymphoma50% in evaluable melanoma patients.
3% in other cohorts
Fatigue (31%), ALT increase (11%), anemia (10%) and AST increase (9%)
GITRMonotherapyTRX-518NCT01239134Solid tumors (melanoma, non- small cell lung and colorectal cancers)14% with irSDCough and fatigue (28% each); vomiting, abdominal pain, and nausea (18% each); dyspnea and anorexia (15% each)
AMG228NCT02437916Solid 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%)
MEDI1873NCT02583165non-small cell lung cancer, head and neck squamous cell carcinoma, colorectal cancer42.5% with SDHeadache (25%) and infusion- related reaction, Grade three nausea/vomiting, and ST elevation myocardial infarction
Monotherapy and combination therapyMK-4166 with or without pembrolizumabNCT02132754Solid tumors and melanoma expansion cohorts9% 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
CD40MonotherapyrhuCD40LSolid tumors and non-Hodgkin's lymphoma6% with PR,
38% with SD
Transient elevations of serum liver transaminases
CP-870,893NCT02225002Solid tumors (melanoma, non-small cell lung cancer, sarcoma, cholangiocarcinoma)14% of all patients and 27% of melanoma patients with PRCRS, transient hematologica; abnormalities, LFT abnormalities
Combination therapyCP-870,893 plus gemcitabinePancreatic cancer19% with PR,
52% with SD
CRS, fatigue, nausea, vomiting, hematologic events
CP-870 to 893 plus paclitaxel and carboplatinNCT00607048Solid 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*ACTRN12609000294257Mesothelioma40% with PRCRS (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.