In Phase I trials, ezabenlimab monotherapy was well tolerated, with a safety profile similar to other PD-1 inhibitors. The maximum tolerated dose was not reached. In these trials, ezabenlimab 240 mg Q3W showed clinical activity in patients with advanced solid tumors, with response rates that are consistent with other PD-1 inhibitors in similar populations.³

Ezabenlimab is currently being investigated in combination regimens across a range of tumor types:

• In combination with DLL3/CD3 T-cell engager (obrixtamig) in patients with advanced SCLC and other NECs expressing DLL3⁴

• In combination with B7-H6/CD3 T-cell engager (BI 765049) in patients with malignant solid tumors expressing B7-H6^5,6

• In combination CD137 FAP agonist antibody (BI 765179) in patients with advanced solid tumors^7–9

• In combination with SIRPα antagonist (BI 770371) in patients with advanced solid tumors^10,11

• In combination with 2^nd generation STING agonist (BI 1703880) in patients with advanced solid tumors¹²

• In combination with VSV-GP oncolytic virus (BI 1831169) in patients with solid tumors¹³

• In combination with the KISIMA® cancer vaccine in patients with pancreatic ductal adenocarcinoma (PDAC)¹⁴

Ezabenlimab clinical trials

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 downregulates immune response. Binding of PD-L1 or PD-L2 inactivates T cells and downregulates the expression of pro-inflammatory cytokines, enabling tumors to evade recognition and elimination by the immune system.^1,2,15

Ezabenlimab is a humanized PD-1-targeting mAb that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2,¹⁵ 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.^1,2,16

Mechanism of action involving immune checkpoint inhibition¹⁵

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.¹⁵

Tumor cells can evade immune surveillance by upregulating PD-L1 expression, which enables them to bind to PD-1 receptors on T cells. This interaction leads to T-cell exhaustion and impairs their ability to effectively recognize and destroy tumor cells.¹⁷

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.¹⁷

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.
CD3, cluster of differentiation 3; CD137, cluster of differentiation 137; DLL3, delta-like canonical Notch ligand 3; FAP, fibroblast activation protein; GP, glycoprotein; MHC, major histocompatibility complex; NEC, neuroendocrine carcinoma; PD-1, programmed cell death protein-1; PD-L1, programmed death ligand-1; PD-L2, programmed death ligand-2; PDAC, pancreatic ductal adenocarcinoma; SCLC, small cell lung cancer; SIRPα, signal regulatory protein alpha; STING, stimulator of interferon genes; TcE, T-cell engager; TCR, T-cell receptor; VSV, vesicular stomatitis virus.