Table 2.
Clinical studies of CD40 agonistic antibodies in cancer treatment, alone or in combination with other treatments.
| Therapy | Interventions | Route of Delivery |
Phase | Cancer Type |
Study/ NCT number |
Status | Dosage (mg /kg) |
Outcome | Side Effects |
|---|---|---|---|---|---|---|---|---|---|
| Selicrelumab | w/w.o nab-paclitaxel and + atezolizumab |
Intra venous,(neo | I | PDAC | NCT02588443 [94] | Completed | 0.2 | OS=23.4 mo, median DFS=1 | Neoadjuvant therapy (n=16): grade 1 CRS (56%). Adjuvant therapy (n=13): grade |
| Intratumoral | Ib | B cell lymphoma | NCT03892525 | Terminated | N/A | N/A | N/A | ||
| CDX-1140 | w/w.o pembrolizumab | Infusion | I | Advanced solid tumor | NCT03329950 [96] | Completed | 0.72 or 1.5 Q3 W | CR (4%) SD (36%) |
At 1.5 mg/kg dose level (n=21): arthralgia (62%), fatigue (62%), nausea (48%), diarrhea (48%), vomiting (43%), myalgia (43%), fever (38%), chills (38%), AST increase (38%), bilirubin increase (24%), ALT increase (19%), CRS (19%) |
| + pembrolizumab | Infusion | I/Ib | Epithelial cancer | NCT04520711 | Completed | N/A | N/A | N/A | |
| + TCRT + radiotherapy + CDX-301 + Poly-ICLC |
Intratumoral | I | Metastatic solid tumors | NCT04616248 | Completed | N/A | N/A | N/A | |
| + CDX-301 | Intravenous injection | I | TNBC | NCT05029999 | Recruiting | 1.5 Q4 W | N/A | N/A | |
| + odetiglucan | N/A | I | PDAC | NCT05484011 | Recruiting | 0.7 2 or 1.5 Q3 W | N/A | N/A | |
| + bevacizumab + pembrolizumab + capecitabine + oxaliplatin + pembrolizumab |
N/A | II | Ovarian cancer | NCT05231122 | Not yet recruiting | N/A | N/A | N/A | |
| Intravenous | I/II | Biliary tract cancer | NCT05849480 | Not yet recruiting | 0.36-1.5 Q3 W | N/A | N/A | ||
| APX 005 M | + nab-paclitaxel and gemcitabine w/w.o nivolumab | Intravenous | II | Pancreatic cance | NCT03214250 [97] | Completed | 0.1 and 0.3 Q4 W | Primary endpoint of 1yr OS met for nivo/chemo (57.7%) but not for sotiga/chemo (48.1%) or sotiga/nivo/chemo (41.3%) | n=105: CRS, infusion reactions, thrombocytopenia and elevated liver function (87% total). CRS in nivo/chemo (0%), sotiga/chemo (24%) and sotiga/nivo/chemo (34%) |
| + domvanalimab + zimberelimab |
Infusion | Ib/II | NCT05419479 | Recruiting | N/A | N/A | N/A | ||
| monotherapy | N/A | I | Pediatric braintumors | NCT03389802 | Ongoing | 0.1 Q3 W | N/A | N/A | |
| + cabirali zumab w/w.o nivolumab | Intravenous infusion | Metastatic melanoma, Kidney cancer, NSCLC | NCT03502330 [98] | Ongoing | 0.03 Q2 W | SD (8%) DP (62%) | n=26: asymptomatic elevations of lactate dehydrogenase (100%), creatine kinase (96%), AST (96%), and ALT (73%); periorbital edema (65%); fatigue (50%); DLT of acute respiratory distress syndrome (3.8%) | ||
| w/w.o radiotherapy | Infusion | II | NCT04337931 | Completed | N/A | N/A | N/A | ||
| + nivolumab | N/A | II | Metastastic melanoma | [99] | Ongoing | 0.3 Q3 W | ORR(15%) PR(13%) SD(36.8%) |
n=38: at least one AE (89%); grade 3 AE related to APX005M (13%): pyrexia, chills, nausea, fatigue, pruritus, elevated liver function, rash, vomiting, headache, arthralgia, asthenia, myalgia, and diarrhea | |
| Mitazalimab | w/w.o corticos teroid pre-infusion | Intravenous | I | Advanced solid tumor | NCT02829099 [102] | Completed | 0.075-2 Q2 W | Mitazalimab has shown to be safe and well tolerated at at doses up to 1.2 mg/kg | n=95: gatigue (44.2%), pyrexia (38.9%), pruritus (38.9%), chills (27.4%), and headache (26.3%). grade-3 or higher TEAEs (56.8%): gamma-glutamyl transferase increase (7.4%), AST increase (5.3%), and anemia (5.3%) |
| + mFOLFIRINOX | Intravenous | Ib/II | mPDAC | NCT04888312 [120] | Ongoing | 0.45 - 0.9 | ORR (52.2%) | n=5, grade 1 or 2 AEs (80%) | |
| + MesoPher + modified FOLFIRINOX |
Intravenous after chemo | I | Metastic pancreatic cancer | NCT05650918 | Rrecruiting | 0.075-0.15 - 0.3-0.6 or 1.2 | N/A | N/A | |
| 2141-V11 | monotherapy | Intratumoral | I | Solid tumor | NCT04059588 [128] | Completed | N/A | N/A | N/A |
| monotherapy | Intravesical instillation | I | Nonmuscle invasive bladder cancer | NCT05126472 [104] | Recruiting | 0.012-0.033-0.12 - 1.2 Q1 W | N/A | N/A | |
| + D2C7-IT | Intratumoral, convection enhanced delivery (CED) | I | Malignant glioma | NCT04547777 [105] | Recruiting | 0.012, 0.033, 0.12 0.35 | Early signs of tumor response (25%) | n=8: headache (grade 3=12.5%; grade 2=25%); paresthesia (grade 3=12.5%; grade 2=12.5%); dysphasia (grade 3 =12.5%); pyramidal tract disorder (grade 3=12.5%; grade 2=12.5%); and depressed level of consciousness (grade 2=12.5%) | |
| SEA-CD40 | monotherapy | Intravenous injection | I | Advanced solid tumors, Lymphoma | NCT02376699 [106] | Terminated | 0.0006, 0.003, 0.01, 0.03, 0.045, 0.06 | 0.03mg/kg was well tolerated | n=67: infusion/hypersensitivity reactions (73%) |
| + nab-paclitaxel and gemcitabine + pembrolizumab |
N/A | I | mPDAC | NCT02376699 [107] | 0.01 or 0.03 Q4 W | OR at 0.01 mg/kg (48%) OR at 0.03 mg/kg (38%) | n=61: fatigue (84%), nausea (74%), and neutropenia (67%); grade ≤3 TEAEs: neutropenia (61%), anemia (33%), and thrombocytopenia (20%); TEAE-caused discontinuation of treatment (10%) | ||
| + carboplatin + pemetrexed + pembrolizumab |
N/A | II | NSCLC Melanoma | NCT04993677 | Ongoing | N/A | N/A | N/A | |
| LVGN7409 | w/w.o LVGN3616 w/w.o LVGN3616 + LVGN6051 | Intravenous infusion | I | Locally advanced, metastatic or recurrent/refract orymalignancy | NCT04635995 [121] | Recruiting | 0.01-0.1, then conventional “3 + 3” design from 0.3 | SD(44%) | n=12: infusion related reaction (58%), amylase increased, lipase increase, ALT increase and AST increase (42% each), bilirubin increase, WBC or neutrophil decrease, nausea, and cytokine release syndrome (8.3% each); grade 3 TRAEs (17%): amylase/lipase increase and ALT/AST increase (8.3% each) |
| monotherapy | Intravenous infusion | I | NCT05152212 | Recruiting | N/A | N/A | N/A | ||
| RO7300490 | w/w.o atezolizumab | I | Intravenous | Advanced solid tumor | NCT04857138 | Recruiting | N/A | N/A | N/A |
| ABBV-428 | w/w.o atezolizumab | Intravenous infusion | I | Advanced solid tumor | NCT02955251 [109] | Completed | 0.01-3.6 | SD at 3.6 mg/kg (36%) | n=59: infusion-related reactions (12%) |
PDAC: pancreatic ductal adenocarcinoma; mPDAC: metastatic pancreatic ductal adenocarcinoma; TNBC: triple-negative breast cancer; NSCLC: non-small cell lung cancer; OS: overall survival; CR: complete response; PR: partial response; SD: stable disease; DFS: disease-free survival; AE: adverse events; TRAE: treatment-related adverse event; CRS: cytokine release syndrome; ALT: aminotransferase; AST: aspartate aminotransferase; WBC: white blood cells.