Drug intelligence / Profile preview

izalontamab brengitecan + pembrolizumab

Development stage
Unknown
Lead developer
SystImmune
Modality
Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Intravenous
01

Overview

Izalontamab brengitecan + pembrolizumab is a combination therapy comprising an innovative **antibody-drug conjugate** (izalontamab brengitecan; also known as Iza-bren) and an immune checkpoint inhibitor (**pembrolizumab**, marketed as Keytruda). **Izalontamab brengitecan** is a bispecific ADC that simultaneously targets **EGFR (epidermal growth factor receptor)** and **HER3 (human epidermal growth factor receptor 3)**, common drivers in various epithelial cancers including non-small cell lung cancer. Upon binding, the ADC exerts dual antitumor activity by blocking receptor signaling and delivering a potent cytotoxic (topoisomerase 1 inhibitor) payload directly into cancer cells, inducing DNA damage and apoptosis. **Pembrolizumab** is a humanized monoclonal antibody targeting **PD-1 (programmed cell death 1)**, blocking its interaction with PD-L1 and PD-L2 to promote antitumor immune response. Combination therapy leverages targeted cytotoxicity and immune checkpoint blockade, potentially enhancing clinical efficacy and overcoming resistance pathways in EGFR- and HER3-driven tumors, especially in previously treated EGFR-mutant NSCLC[2][5][6][8].

02

Targets

EGFR T790M (Epidermal growth factor receptor T790M mutant)PDCD1 (Programmed cell death protein 1 receptor)TOP1 (DNA Topoisomerase I)ERBB3 (Erb-b2 receptor tyrosine kinase 3)

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