Table 1

List of CD27/CD70 targeting antibodies tested in clinical trials

Name of the compoundMechanism of actionTumour typePhase of clinical trial developmentCompanyClinical benefit rate=
(CR+PR+SD)/
n (%)
Most common side effectsReference/trial number
Varlilumab, CDX-1127Fully human IgG1 CD27 agonistic mAbHaematological and solid cancersPhase I, completedCelldex Therapeutics9/56=16.1%Fatigue (54%), nausea (30%), dyspnoea (25%)Burris et al/NCT0146013440
SGN-75Humanised anti-CD70 IgG1 mAb linked to MMAF toxinRCC, NHLPhase I, completedSeattle Genetics23/58=39.7%Fatigue (40%), dry eye (32%), nausea (30%), thrombocytopenia (26%)Tannir et al/NCT0101591121
SGN-75+everolimusHumanised anti-CD70 IgG1 mAb linked to MMAF toxin+mTOR inhibitorRCCPhase I, terminated (reason: not available)Seattle Geneticsn/an/aNCT01677390
SGN-CD70AADC directed against CD70 antigen with the cytotoxic component PBDRCC, Mantle-Cell lymphoma, diffuse large B-cell lymphoma, grade 3 follicular lymphomaPhase I, completedSeattle GeneticsRCC: 14/18=77.8%
Lymphoma: 4/20=20%
RCC: fatigue (67%), anaemia (61%), thrombocytopenia (56%)
Lymphoma: thrombocytopenia (75%), nausea (55%), anaemia (50%), fatigue (50%)
Pal et al, Phillips et al/NCT0221689044 49
AMG 172Humanised anti-CD27L IgG1 mAb linked to MCC-DM1RCCPhase I, completedAmgen8/37=21.6%Thrombocytopenia (59%), nausea (54%), decreased appetite (49%), vomiting (46%), fatigue (35%)Massard et al/NCT0149782145
ARGX-110 (Cusatuzumab)Glycoengineered CD70 blocking mAbAdvanced cancersPhase I, active, not recruitingArgenx BVBA14/26=53.8%Fatigue (65%), drug-related infusion-related reactions (38%), dyspnoea (31%), fever (31%)Aftimos et al/NCT01813539+NCT0275925046
MDX-1203, BMS-936561ADC of humanised CD70-mAb linked to MED-2460RCC, NHLPhase I, completedBMS18/26=69.2%Fatigue (85%), nausea (54%), decreased appetite (39%)Owonikoko et al/NCT0094490548
Varlilumab+
nivolumab
Fully human IgG1 CD27 agonistic mAb+fully human IgG4 mAb targeting PD-1SCCHN, ovarian cancer, colorectal cancer, RCC, glioblastomaPhase I/II, completedCelldex Therapeutics and BMSOVA Ca: 24/49=49.0%
CRC: 9/41=22.0%
OVA Ca: pruritus (18%), rash (18%), infusion reaction (17%)
CRC: infusion reaction (31%), nausea (17%), lymphopenia (17%)
Sanborn et al/NCT0233591842
Varlilumab+
sunitinib
Fully human IgG1 CD27 agonistic mAb+small molecule inhibiting multiple receptor tyrosine kinasesRCC, urogenital neoplasmsPhase I, terminated (reason: portfolio reprioritisation)Celldex Therapeuticsn/an/aNCT02386111
Varlilumab+
ipilimumab+CDX-1401
Fully human IgG1 CD27 agonistic mAb+human mAb blocking CTLA-4+immunomodulating vaccine made of fully human mAb linked to NY-ESO-1 in combination with poly-ICLC (Hiltonol)Unresectable Stage III or stage IV melanomaPhase I/II, terminated (reason: feasibility concerns due to changes in standard of care)Celldex Therapeuticsn/an/aNCT02413827
Varlilumab+
ONT-10
Fully human IgG1 CD27 agonistic mAb+liposomal synthetic glycopolypeptide vaccine MUC1 targeted antigen formulated with PET lipid A adjuvantBreast cancer, ovarian cancerPhase Ib, completedCascadian Therapeutics+
Celldex Therapeutics
n/an/aNCT02270372
TriMix-DC+
TLR-DC
Autologous dendritic cell vaccineMelanomaPhase I/II, completedRadboud University8/15=53.3%Local skin injection site reactions: irritation, erythema, swelling (100%), flu-like symptoms (53%), chills (20%), fever (20%)Wilgenhof et al/NCT0153069850
  • ADC, antibody drug conjugate; CD27, cluster of differentiation 27; CD70, cluster of differentiation 70; CR, complete response; CRC, colorectal cancer; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; DC, dentritic cell; mAb, monoclonal antibody; MCC-DM1, 4-[N-maleimidomethyl] cyclohexane-1-carboxylate + maytansine; MMAF, monomethyl auristatin F; mTor, mammalian target of rapamycin; MUC1, mucin 1; n/a, not available; NHL, non-Hodgkin's lymphoma; NY-ESO-1, New York esophageal squamous cell carcinoma-1; OVA Ca, ovarian cancer; PBD, pyrrolobenzodiazepine; PD-1, programmed cell death 1; poly-ICLC, polyinosinic-polycytidylic acid stabilised with polylysine and carboxymethyl cellulose; PR, partial response; RCC, renal cell carcinoma; RT, radiotherapy; SCCHN, squamous cell carcinoma of the head and nNeck; SD, stable disease; TLR, toll-like receptor.