Table 3.
Clinical trials of drugs for the treatment of colorectal cancer (United States National Library of Medicine; ClinicalTrials.gov)
|
Clinical trials (phase)
|
Drug
|
Target
|
Mechanism of action
|
| Antisense oligonucleotides | |||
| NCT00844064 (I) | AP12009 (trabedersen) | TGF-β2 | By binding to TGF-βII mrna, its expression is reduced |
| Antibodies | |||
| NCT04952753 (II) | NIS793 | TGF-β | Reduction of active cytokine, reduction of SMAD2/3 phosphorylation, and reduction of TGF-β target gene expression |
| NCT02947165 (I) | NIS793 | TGF-β | Reduction of active cytokine, reduction of SMAD2/3 phosphorylation, and reduction of TGF-β target gene expression |
| NCT01646203(I) | IMC-TR1 | TGF-βRII | Reduction of active cytokine, reduction of SMAD2/3 phosphorylation, and reduction of TGF-β target gene expression |
| Ligand traps | |||
| NCT03436563 (I/II) | M7824 | TGF-βRII | Bifunctional anti-PD-L1/TGF-βRII trap fusion protein |
| NCT02517398(I) | Bintrafusp alfa | TGF-βRII and PD-L1 | First-in-class bifunctional fusion protein composed of a mab against PD-L1 fused to the extracellular domain of the TGF-β receptor II |
| NCT04856787 (II/III) | SHR-1701 | TGF-βRII | Bifunctional anti-PD-L1/TGF-βRII agent |
| Small molecule receptor kinase inhibitors | |||
| NCT04031872 (I/II) | LY3200882; capecitabine | TGF-βRI | By blocking ATP binding to TGF-βR, receptor kinase activity and signal transduction are reduced |
| NCT05400122 (I) | Vactosertib | TGF-βRI | Inhibits the activity of TGF-βR1 |
| NCT03724851 (I/II) | Vactosertib + Pembroli-zumab | TGF-βRI | Inhibits the activity of TGF-βR1 |
| NCT03470350 (I/II) | Galunisertib | TGF-βRI | Inhibits the activity of TGF-βR1 |
| Immune checkpoints | |||
| NCT04540159 | TGF-β1 | Measuring the level Active TGF-β1 by flow-cytometric analysis in the intraabdominal ascites | |
| Adoptive cell therapy | |||
| NCT03431311 (I/II) | ACT | TGF-βII | ACT with Radium-1 TCR + T cells transiently redirected against the TGF-βRII frameshift antigen which is expressed in MSI+ colon cancer. |
| NCT05040568 (I) | CB-NK-TGF-βR2-/NR3C1 | Immunotherapy with ex vivo preactivated and expanded CB-NK cells in combination with cetuximab | |
ACT: Adoptive cell therapy; TGF: Transforming growth factor.