ezabenlimab (PD-1 inhibitor)
A humanized PD-1-targeting monoclonal antibody that blocks the interaction between PD-1 and its ligands
![Xentuzumab](/us/inoncology/sites/default/files/2021-10/xentuzumab-bg.png)
ezabenlimab: a PD-1 inhibitor
Ezabenlimab* is a humanized programmed cell death protein-1 (PD-1)-targeting monoclonal antibody (mAb) that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.1
Clinical trials (monotherapy and combinations): ezabenlimab is being investigated as a monotherapy for solid tumors in a Phase I trial.2 Phase I and II trials of ezabenlimab in combination with brigimadlin [BI 907828] (a murine double minute 2 [MDM2]-p53 antagonist),*3 BI 765049 (a B7-H6/CD3 T-cell engager),*4 BI 765179 (a CD137 FAP agonist),*5 signal-regulatory protein alpha [SIRPα] antagonists,*6-9 VSV-GP,*10 KISIMA™ cancer vaccine,*11 and BI 1703880 (a STING agonist)*12 are ongoing.
*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.
Role of PD-1
PD-1 is an inhibitory cell surface receptor that is activated by inflammatory signals. It has two known ligands, PD-L1 and PD-L2, which are both expressed on antigen-presenting cells. In normal tissues, binding of PD-L1 or PD-L2 to PD-1 inhibits T cell receptor signaling, limiting T cell function and preventing immune-mediated damage to healthy cells and tissues.12
Tumor cells can avoid destruction by host-immune surveillance. One mechanism that tumor cells use to avoid immune-mediated destruction is to upregulate PD-L1 expression, which leads to inactivation of PD-1-expressing T cells.13
Preclinical studies and clinical trials have shown that immunotherapeutic approaches using antibodies to block pathways, such as the PD-1 pathway, can enhance the immune system’s antitumor activity in the fight against cancer.13
About ezabenlimab
Mechanism of action
The PD-1 receptor is found on T cells, B cells, monocytes and natural killer cells. Activation of the PD-1 pathway by its ligands PD-L1 and PD-L2 negatively regulates immune response.1 Binding of PD-L1 or PD-L2 inactivates T cells and downregulates the expression of pro-inflammatory cytokines, enabling tumors to evade elimination.12
Ezabenlimab is a humanized PD-1-targeting mAb that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2,1 thereby inhibiting downstream PD-1 signaling. This allows T cells to remain active and to carry out their role in the destruction of tumor cells by secreting molecules such as perforin and granzyme B.1,14
Mechanism of action involving immune checkpoint inhibition1
![Mechanism of action involving immune checkpoint inhibition Mechanism of action involving immune checkpoint inhibition](/us/inoncology/sites/default/files/2024-05/ezabenlimab%20moa%20image.png)
MHC, major histocompatibility complex; PD-1, programmed cell death protein-1; PD-L1, programmed death ligand-1; TCR, T-cell receptor.
Clinical development
Ezabenlimab is currently being investigated in combination regimens across a range of tumor types:
- In combination with brigimadlin (MDM2-p53 antagonist) in patients with advanced solid tumors3
- In combination with B7-H6/CD3 T-cell engager (BI 765049) in patients with advanced solid tumors expressing B7-H64
- In combination CD137 FAP agonist (BI 765179) in patients with advanced solid tumors5
- In combination with SIRPα antagonist (BI 765063) in patients with solid tumors6-8
- In combination with SIRPα antagonist (BI 770371) in patients with advanced solid tumors9
- In combination with VSV-GP oncolytic virus (BI 1831169) in patients with solid tumors10
- In combination with the KISIMA™ cancer vaccine in patients with pancreatic ductal adenocarcinoma11
- In combination with 2nd generation STING agonist (BI 1703880) in patients with advanced solid tumors12
ezabenlimab clinical trials
Trial number | Phase | Treatment | Patient population | Status |
---|---|---|---|---|
I | brigimadlin (MDM2-p53 antagonist) + ezabenlimab | Advanced solid tumors | Recruiting | |
I | B7-H6/CD3 TcE (BI 765049) ± ezabenlimab | Advanced solid tumors expressing B7-H6 | Recruiting | |
I | CD137 FAP agonist (BI 765179) ± ezabenlimab | Advanced solid tumors | Recruiting | |
I | SIRPα antagonist (BI 765063) ± ezabenlimab | Advanced solid tumors that have a SIRPα polymorphism, including at least one V1 allele | Completed recruitment | |
I | SIRPα antagonist (BI 765063) ± ezabenlimab alone or with BI 836880, chemotherapy, or cetuximab | Recurrent/metastatic HNSCC or HCC | Recruiting | |
I | SIRPα antagonist (BI 765063 or BI 770371) in combination with ezabenlimab | Advanced HNSCC, NSCLC, or melanoma | Recruiting | |
I | SIRPα antagonist (BI 770371) ± ezabenlimab | Advanced solid tumors | Recruiting | |
I | VSV-GP (BI 1831169) ± ezabenlimab | Solid tumors | Recruiting | |
NCT05846516 (KISIMA-02)11 | I | KISIMA™ cancer vaccine (ATP150/ATP152), VSV-GP154, ezabenlimab (PD-1 inhibitor) | PDAC | Recruiting |
I | STING agonist (BI 1703880) ± ezabenlimab | Advanced solid tumors | Recruiting |
CRC, colorectal cancer; GP, glycoprotein; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinoma; NSCLC, non-small cell lung cancer; PD-1, programmed death-1 receptor; PD-L1, programmed death-1 receptor ligand; SIRPα, signal-regulatory protein alpha; TcE, T-cell engager; VSV, vesicular stomatitis virus.
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