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izalontamab brengitecan (Hansoh Pharmaceutical Group)
- Development stage
- Unknown
- Lead developer
- Bristol Myers Squibb
- 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 (HS-20093, GSK5764227) is an antibody-drug conjugate (ADC) targeting B7-H3 (CD276), a transmembrane protein overexpressed in various solid tumors, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). It consists of a humanized anti-B7-H3 monoclonal antibody (izalontamab) covalently linked to a topoisomerase I inhibitor payload (brengitecan) via a protease-cleavable linker. The mechanism involves the binding of the antibody to B7-H3 on the tumor cell surface, followed by internalization and release of the cytotoxic payload, which induces DNA damage and cell death. Originally developed by Hansoh Pharmaceutical, the drug was licensed to GSK in December 2023 for global development and commercialization (excluding Greater China). It is currently being evaluated in Phase 1 and Phase 2 trials, including the IZA-A trial which investigates its combination with the KRAS G12C inhibitor adagrasib in patients with advanced KRAS-mutant NSCLC.
- Other names
- IZA-BRENIZA-B
02
Targets
TOP1 (DNA Topoisomerase I)EGFR T790M (Epidermal growth factor receptor T790M mutant)ERBB3 (Erb-b2 receptor tyrosine kinase 3)
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