Header

ezabenlimab (PD-1 inhibitor)

A humanized PD-1-targeting monoclonal antibody that blocks the interaction between PD-1 and its ligands

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

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:

ezabenlimab clinical trials

Trial numberPhaseTreatmentPatient populationStatus

NCT03964233 (1403-0002)3

I

brigimadlin (MDM2-p53 antagonist) + ezabenlimab 

Advanced solid tumors

Recruiting

NCT04752215 (1454-0001)4

I

B7-H6/CD3 TcE (BI 765049) ± ezabenlimab

Advanced solid tumors expressing B7-H6

Recruiting

NCT04958239 (1463-0001)5

I

CD137 FAP agonist (BI 765179) ± ezabenlimab

Advanced solid tumors

Recruiting

NCT03990233 (1443-0001)6

I

SIRPα antagonist (BI 765063) ± ezabenlimab

Advanced solid tumors that have a SIRPα polymorphism, including at least one V1 allele

Completed recruitment

NCT05249426 (1443-0002)7

I 

SIRPα antagonist (BI 765063) ± ezabenlimab alone or with BI 836880, chemotherapy, or cetuximab

Recurrent/metastatic HNSCC or HCC 

Recruiting 

NCT05068102 (1443-0003)8

I

SIRPα antagonist (BI 765063 or BI 770371) in combination with ezabenlimab

Advanced HNSCC, NSCLC, or melanoma

Recruiting

NCT05327946 (1501-0001)9 

I 

SIRPα antagonist (BI 770371) ± ezabenlimab

Advanced solid tumors 

Recruiting 

NCT05155332 (1456-0001)10

I 

VSV-GP (BI 1831169) ± ezabenlimab 

Solid tumors

Recruiting 

NCT05846516 (KISIMA-02)11IKISIMA™ cancer vaccine (ATP150/ATP152), VSV-GP154, ezabenlimab (PD-1 inhibitor)PDACRecruiting

NCT05471856 (1480-0001)12

ISTING agonist (BI 1703880) ± ezabenlimabAdvanced solid tumorsRecruiting

 
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.

You may also be interested in…

  1. Zettl M, et al. Cancer Res. 2018;78(Suppl. 13): Abstract 4558 and poster.

  2. ClinicalTrials.gov. NCT02952248. https://clinicaltrials.gov/study/NCT02952248 (Accessed: February 2024).

  3. ClinicalTrials.gov. NCT03964233. https://clinicaltrials.gov/study/NCT03964233 (Accessed: February 2024).

  4. ClinicalTrials.gov. NCT04752215. https://clinicaltrials.gov/study/NCT04752215 (Accessed: February 2024).

  5. ClinicalTrials.gov. NCT04958239. https://clinicaltrials.gov/study/NCT04958239 (Accessed: February 2024).

  6. ClinicalTrials.gov. NCT03990233. https://clinicaltrials.gov/study/NCT03990233 (Accessed: February 2024).

  7. ClinicalTrials.gov. NCT05249426. https://clinicaltrials.gov/study/NCT05249426 (Accessed: February 2024).

  8. ClinicalTrials.gov. NCT05068102. https://clinicaltrials.gov/study/NCT05068102 (Accessed: February 2024).

  9. ClinicalTrials.gov. NCT05327946. https://clinicaltrials.gov/study/NCT05327946 (Accessed: February 2024).

  10. ClinicalTrials.gov. NCT05155332. https://clinicaltrials.gov/study/NCT05155332 (Accessed: February 2024).

  11. ClinicalTrials.gov. NCT05846516. https://clinicaltrials.gov/study/NCT05846516 (Accessed: February 2024).

  12. ClinicalTrials.gov. NCT05471856. https://clinicaltrials.gov/study/NCT05471856 (Accessed: February 2024).

  13. McDermott DF, et al. Cancer Med. 2013;2(5):662–73. 

  14. He J, et al. Sci Rep. 2015;5:13110.

  15. Martinez-Lostao L, et al. Clin Cancer Res. 2015;21(22):5047–56.

Share this page