Ezabenlimab (BI 754091)

PD-1 inhibitor (BI 754091)

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 currently being investigated as a monotherapy in a Phase I trial in solid tumors.2  Phase I and II trials of ezabenlimab in combination with BI 836880*3–5 (a vascular endothelial growth factor/angiopoietin-2 growth factor [VEGF/Ang2] inhibitor), BI 765063*6 (a signal-regulatory protein alpha [SIRPα] antagonist), BI 1387446*7 (a STING agonist), BI 907828 (a murine double minute 2 [MDM2]-p53 antagonist),*8 and the KISIMA™ cancer vaccine (ATP-128)*9 are also ongoing.

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.10

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.11

Preclinical studies and clinical trials have shown that immunotherapeutic approaches using antibodies to block pathways, such as the PD-1 pathway, can facilitate the immune system’s antitumor activity in the treatment of cancers.11

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.10

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.1,12

Mechanism of action involving immune checkpoint inhibition1

PD-1 inhibitor mechanism of action
MHC, major histocompatibility complex; PD-1, programmed cell death protein-1; PD-L1, programmed death ligand-1; TCR, T-cell receptor.

Combination therapy

There is mechanistic rationale and preclinical data to suggest the potential for synergistic effects of ezabenlimab when used in combination with the humanized bispecific nanobody® BI 836880 (which comprises blocking domains for VEGF and Ang2).13

Clinical development

Ezabenlimab is currently being investigated as a monotherapy in patients with solid tumors and as part of the following combination regimens across a range of tumor types:

  • In combination with the VEGF/Ang2 inhibitor BI 836880 in patients with NSCLC and other solid tumors3–5
  • In combination with the SIRPα antagonist BI 765063 in patients with solid tumors6
  • In combination with the STING agonist BI 1387446 in patients with advanced solid tumors7
  • In combination with the MDM2-p53 antagonist BI 907828 in patients with advanced solid tumors8
  • In combination with the KISIMA™ cancer vaccine (ATP-128) in patients with Stage IV colorectal cancer7

More information about Boehringer Ingelheim oncology clinical trials can be found on the MyStudyWindow website. Relevant trials for ezabenlimab include: BI 1381-0009 and BI 1336-0011.

Ezabenlimab clinical trials

Trial number Phase Treatment Patient population Status

NCT029522482 (1381.1)


Ezabenlimab (BI 754091)

Advanced, unresectable and/or metastatic solid tumors refractory to or unsuitable for standard therapies (Phase Ia)


Selected advanced, unresectable and/or metastatic solid tumors (Phase Ib)

Active, not recruiting

NCT036973045 (1381.9)


Ezabenlimab (BI 754091) + VEGF/Ang2 inhibitor (BI 836880)

Advanced or metastatic solid tumors (i.e. gastric adenocarcinoma or GEC; primary/secondary PD-1-resistant tumors; MSS CRC; or MMRp/MSS endometrial tumors)


NCT034684263 (1336.11)


Ezabenlimab (BI 754091) + VEGF/Ang2 inhibitor

(BI 836880)

Locally advanced or metastatic non-squamous NSCLC with PD-L1 expression >1% by IHC


NCT039721504 (1336.12)


Ezabenlimab (BI 754091) + VEGF/Ang2 inhibitor

(BI 836880)

Japanese patients with advanced, unresectable, and/or metastatic solid tumors

Active, not recruiting

NCT039902336 (1443.1)


BI 765063 (monotherapy and in combination with ezabenlimab)

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


NCT040464459 (KISIMA-01)


KISIMA™ cancer vaccine (ATP-128) (monotherapy and in combination with ezabenlimab)

Histologically or cytologically confirmed Stage IV CRC


NCT041472347 (1426.1)


STING agonist (monotherapy and in combination with ezabenlimab)

Advanced solid tumors


NCT039642338 (1403.2)


BI 907828 + ezabenlimab

Advanced solid tumors


Ang2, angiopoietin 2; CRC, colorectal cancer; GEC, gastro-esophageal adenocarcinoma; IHC, immunohistochemistry; MSS, microsatellite stable; NSCLC, non-small cell lung cancer; PD-1, programmed death-1 receptor; PD-L1, programmed death-1 receptor ligand; MMRp, mismatch repair proficient; SIRPα, signal-regulatory protein alpha; VEGF, vascular endothelial growth factor.

Explore our latest ezabenlimab data

Our latest data on our ezabenlimab were presented at the European Society for Medical Oncology (ESMO) , Association for Cancer Research (AACR) and American Society for Clinical Oncology (ASCO) Congresses 2020,  as well as the ASCO Gastrointestinal Cancers Symposium 2021.




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


ClinicalTrials.gov. NCT02952248. https://clinicaltrials.gov/ct2/show/NCT02952248 (Accessed: February 2021).


ClinicalTrials.gov. NCT03468426. https://clinicaltrials.gov/ct2/show/NCT03468426 (Accessed: February 2021).


ClinicalTrials.gov. NCT03972150. http://clinicaltrials.gov/ct2/show/NCT03972150 (Accessed: February 2021).


ClinicalTrials.gov. NCT03697304. https://clinicaltrials.gov/ct2/show/NCT03697304 (Accessed: February 2021).


ClinicalTrials.gov. NCT03990233. https://clinicaltrials.gov/ct2/show/NCT03990233 (Accessed: February 2021).


ClinicalTrials.gov. NCT04147234. https://clinicaltrials.gov/ct2/show/NCT04147234 (Accessed: February 2021).


ClinicalTrials.gov. NCT03964233. https://clinicaltrials.gov/ct2/show/NCT03964233 (Accessed: March 2021).


ClinicalTrials.gov. NCT04046445. https://clinicaltrials.gov/ct2/show/NCT04046445 (Accessed: February 2021).


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


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


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


Hofmann I, et al. Poster presentation at the 8th Euro Global Summit on Cancer Therapy 2015.

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.


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Page last updated: March 2021