Table 5.
Summary of clinical efficacy of CD40/CD40L-targeted therapy
| Drug | Feature | Disease | Efficacy, n (%) | PMID |
|---|---|---|---|---|
| Malignancy (single agent) | ||||
| CP-870,893 | CD40 agonistic human mAb | Solid tumors | PR: 4 (27%) in melanoma | 17327609 |
| Dacetuzumab | CD40 agonistic humanized mAb | Refractory NHL | CR: 1 (2%); PR: 5 (10%); SD:13 (26%) | 19636010 |
| Relapsed DLBCL | CR: 2 (4%); PR: 2 (4%); SD:13 (28%) | 24919462 | ||
| Avrend | Trimeric soluble human CD40L | Advanced solid tumors and NHL | CR: 1 (3%); PR: 1 (3%); SD: 4 (12%) | 11432896 |
| Lucatumumab | CD40 antagonistic human mAb | Relapsed MM | PR: 1 (4%); SD: 12 (43%) | 22861192 |
| Advanced lymphoma | FL: CR: 1 (4.8%); PR: 6 (28.6%); SD:11 (52.4%); DLBCL: CR: 2 (5.9%); PR: 2 (5.9%); SD:11 (32.4%); MALT: CR: 1 (14.3%); PR: 2 (28.6%); SD:1 (14.3%); MCL: SD: 5 (41.7%); HL: PR: 5 (13.5%); SD:12 (32.4%) | 24219359 | ||
| Malignancy (combinatory therapy) | ||||
| CP-870,893+gemcitabine | +chemotherapy | Advanced pancreatic ductal adenocarcinoma | PR: 4 (18.2%) | 23983255 |
| CP-870,893+gemcitabine | +chemotherapy | Advanced pancreatic ductal adenocarcinoma | PR: 4 (19%); SD: 11 (52.4%) | 2143645 |
| CP-870,893+tremelimumab | +CTLA4 antagonistic mAb | Metastatic melanoma | CR: 2 (9.1%); PR: 4 (18.2) | 30288340 |
| Dacetuzumab+rituximab+gemcitabine | + CD20 antagonistic mAb+chemotherapy | Relapsed DLBCL | CR: 6 (20%); PR: 8 (27%); SD:13 (28%) | 22775314 |
| Autoimmunity | ||||
| ch5D12 | CD40 antagonistic chimeric mAb | Crohn’s disease | CRR: 13 (72%) | 16011669 |
| Iscalimab | CD40 antagonistic human mAb | Grave’s disease | CRR: 7 (47%) | 31512728 |
| Dapirolizumab | CD40L antagonistic humanized mAb Fab | Systemic lupus erythematosus | CRR: 11 (46%) | 28780512 |
| VIB4920 | CD40L antagonist human protein | Rheumatoid arthritis | CRR: 8 (75%) in the 1500-mg group and 6 (50%) in 1000-mg | 31019027 |
Abbreviations: CD40L, CD40L ligand; CR: complete response; CRR: clinical response rate; CTLA4: cytotoxic T-Lymphocyte associated protein 4; DLBCL: diffuse large B-cell lymphoma; Fab, antigen-binding fragment; FL: follicular lymphoma; HL: Hodgkin lymphoma; mAb: monoclonal antibody; MALT: mucosa associated lymphatic tissue lymphoma; MCL: mantle cell lymphoma; PR: partial response; SD: stable disease.