Table 1.
Novel immune checkpoint inhibitors and ongoing clinical trials.
| Target | Proposed function | Drug | ClinicalTrials.gov Identifier | Phase |
|---|---|---|---|---|
| TIGIT | Inhibitory receptor on activated T-cells that binds to CD155 and CD112 on tumor cells | Tiragolumab (anti TIGIT mAb) |
NCT04256421 NCT04294810 NCT04513925 NCT04619797 NCT04832854 NCT04308785 |
III III III II II II |
| Vibostolimab (anti TIGIT mAb) |
NCT04738487 NCT02964013 |
III I |
||
| Domvanalimab (anti TIGIT mAb) |
NCT04736173 NCT04262856 NCT04791839 |
III II II |
||
| LAG 3 | Inhibitory co-receptor in T-cell stimulation | Eftilagimod alpha (soluble LAG-3 fusion protein) | NCT03625323 | II |
| Relatlimab (anti LAG3 mAb) | NCT04623775 | II | ||
| BI 754111 (anti LAG3 mAb) | NCT03156114 | I | ||
| TIM-3 | Inhibitory receptor on CD4+ and CD8+ cells that causes Th1 suppression | RO7121661 (bispecific anti TIM-3/anti-PD1 mAb) | NCT03708328 | I |
| MGB453 (anti-TIM3-mAb) | NCT02608268 | I | ||
| TSR-022 (anti-TIM-3 mAb) | NCT03307785 | I | ||
| NKG2A | Inhibitory receptor on NK and CD8+ T cells | Monalizumab (anti NKG2A mAb) |
NCT03833440 NCT03822351 NCT05061550 |
II II II |
| CD73 | Generates adenosine which suppresses immune activation through A2A receptor | Oleclumab (anti CD73 mAb) |
NCT05061550 NCT03822351 NCT03334617 |
II II II |
| IDO-1 | Enzyme on tumor cells that metabolizes tryptophan to kynurenine and subsequently inhibits T-cell differentiation | LY3381916 (IDO-1 inhibitor) | NCT03343613 | I |
| Epacadostat (IDO-1 inhibitor) |
NCT03322540 NCT03322566 |
II II |
||
| Indoximod (IDO-1 inhibitor) | NCT02460367 | I | ||
| B7-H3 | Inhibitor of CD4+ and CD8+ cells, decreases IL2 and IFN- γ production | Enoblituzumab (anti B7-H3 mAb) |
NCT02381314 NCT02475213 |
I I |
| CD27 | Expressed on T-cells; agonism thought to stimulate effector T-cells and repress T-regs | Varlilumab (anti-CD27 mAb) |
NCT01460134 NCT04081688 |
I I |
| GITR | GITR receptor binding with GITR-ligand promotes tumor cell apoptosis and increased activity of T-cells and NK cells | MEDI1873 (GITRL/IgG1 agonist fusion protein) | NCT02583165 | I |
| BMS-986156 (IgG1 agonist mAb to GITR) | NCT04021043 | I/II | ||
| CD47 and SIRPα | CD47 (overexpressed on tumor cells) binds to SIRPα receptor on myeloid cells and restricts phagocytosis | TTI-621(soluble recombinant fusion protein against CD47) | NCT02663518 | I |
| Magrolimab (anti CD47 mAb) | NCT04827576 | II | ||
| VISTA | Homologous to PD-L1; suppresses T-cell proliferation | CA-170 (oral PD-L1, PD-L2 and VISTA checkpoint antagonist) | NCT02812875 | I |
TIGIT, T cell immunoreceptor with Ig and ITIM domains; mAb, monoclonal antibody; LAG-3, Lymphocyte activation gene 3; TIM-3, T-cell immunoglobulin and mucin-domain containing-3; NKG2A, NK group 2 member A; CD73, Cluster of differentiation 73; IDO1, Indoleamine 2, 3-dioxygenase 1; B7-H3, B7 homolog 3; IFN- γ, Interferon Gamma; CD27, Cluster of differentiation 27; GITR, glucocorticoid-induced TNFR-related receptor; CD47 and SIRPα, Cluster of differentiation 47 and Signal Regulatory Protein Alpha; VISTA, V-domain immunoglobulin suppressor of T cell activation; IL-2, Interleukin 2; T-regs, Regulatory T-cells; NK cells, Natural Killer Cells; PD-L1, Programmed Death-Ligand 1.