Table 3.
Inhibitory and stimulatory immune checkpoint molecules with respective anti-receptor antagonistic antibodies and examples of clinical trials.
| Receptor | Antagonistic Compounds | Example Clinical Trials (Phase) | Comments |
|---|---|---|---|
| Inhibitory immune checkpoint molecules | |||
| LAG-3 | MGD013 (Anti-PD-1, anti-LAG-3 dual checkpoint inhibitor) | NCT04082364 (Phase 2/3) | HER2-positive gastric cancer or gastroesophageal junction cancer to determine the efficacy of margetuximab combined with anti-HER2 monoclonal antibody and margetuximab combined with anti-HER2 monoclonal antibody or MGD013 and chemotherapy compared to trastuzumab combined with chemotherapy (Cohort B) |
| Relatlimab (BMS-986016) | NCT01968109 (Phase 1) | Administered alone and in combination with nivolumab in patients with solid tumors: non-small cell lung cancer, gastric cancer, hepatocellular carcinoma, renal cell carcinoma, bladder cancer, squamous cell carcinoma of the head and neck, and melanoma. | |
| TIGIT | BGB-A1217 | NCT04047862 (Phase 2) | Evaluation of anti-tumor effect of BGB-A1217 in combination with tislelizumab in patients with advanced solid tumors. |
| BMS-986207 | NCT02913313 (Phase 1/2a) | Advanced or spread solid cancers. Administered alone and in combination with nivolumab |
|
| TIM-3 (HAVcr2) | Sym023 | NCT03489343 (Phase 1) | As a monotherapy in patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas |
| TSR-022 | NCT02817633 (Phase 1) | As a monotherapy and in combination with an anti-PD-1 antibody and/or an anti-LAG-3 antibody, in patients with advanced solid tumors | |
| MBG453 | NCT03961971 (Phase 1) | MBG453 with stereotactic radiosurgery and spartalizumab in treating patients with recurrent glioblastoma multiforme | |
| NCT03066648 (Phase 1) | As a monotherapy and in combination with an anti-PD-1 antibody (PDR001) and/or Decitabine in acute myeloid leukemia and high risk myelodysplastic syndromes patients | ||
| VISTA | JNJ-61610588 | NCT02671955 (Phase 1) | Evaluation the safety and tolerability of JNJ-61610588 in participants with advanced cancer—study terminated. |
| CEACAM1 | CM-24 (MK-6018) | NCT02346955 | Advanced or recurrent malignancies, administered as monotherapy or in combination with pembrolizumab—study terminated. |
| Stimulatory immune checkpoint molecules | |||
| CD28 | Theralizumab (TAB08) | NCT03006029 (Phase 1) | Metastatic or unresectable advanced solid malignancies |
| OX40 (CD134) | BMS 986178 | NCT03831295 (Phase 1) | Advanced solid malignancies, combination with TLR9 agonist SD-101 |
| MEDI6469 | NCT02274155 (Phase 1) | Head and neck squamous cell carcinoma | |
| PF-04518600 | NCT03971409 (Phase 2) | Triple negative breast cancer, combination with nivolumab | |
| GSK3174998 | NCT02528357 (Phase 1) | Advanced solid tumors, combination with pembrolizumab | |
| MOXR0916 | NCT02219724 (Phase 1) | Locally advanced or metastatic solid tumors | |
| 4-1BB (CD137) | Utomilumab (PF-05082566) | NCT03364348 (Phase 1) | Advanced HER2-positive breast cancer, combination with trastuzumab |
| NCT02179918 (Phase 1) | Advanced solid tumors, combination with PD-1 inhibitor MK-3475 | ||
| Urelumab (BMS-663513) ES101 | NCT02534506 (Phase 1) | Advanced malignancies, alone or in combination with nivolumab | |
| NCT04009460 (Phase 1) | Advanced solid tumors, anti-PD-L1/4-1BB bispecific antibody | ||
| GITRL | BMS-986156 | NCT02598960 (Phase 1/2) | Advanced solid tumors, alone or with nivolumab |
| TRX-518 | NCT01239134 (Phase 1) | Solid malignancies | |
| NCT02628574 (Phase 1) | Advanced solid tumors, in combination with gemcitabine, pembrolizumab, or nivolumab | ||
| AMG 228 | NCT02437916 (Phase 1) | Advanced solid tumors | |
| ICOSLG, (CD275) | JTX-2011 | NCT02904226 (Phase 1/2) | Advanced solid malignancies, alone or in combination with nivolumab |
| GSK3359609 | NCT02723955 (Phase 1) | Advanced solid tumors, alone or in combination with pembrolizumab | |
| BMS-986226 | NCT03251924 (Phase 1/2) | Advanced solid tumors, alone or in combination with nivolumab or ipilimumab | |
| MEDI-570 | NCT02520791 (Phase 1) | T-cell lymphomas, antagonistic antibody | |
| CD27 | Varlilumab (CDX-1127) | NCT04081688 (Phase 1) NCT02335918 (Phase 1/2) | Non-small cell lung carcinoma, combination with atezolizumab and radiation therapy Five types of solid tumors, combination with nivolumab |