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tacabrutideg + zanubrutinib
- Development stage
- Phase 2
- Lead developer
- BeiGene
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Oral
01
Overview
Tacabrutideg + BRUKINSA is an investigational combination regimen being developed by BeOne Medicines (formerly BeiGene) for the treatment of B-cell malignancies, including relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), and Waldenström's macroglobulinemia (WM). The regimen pairs tacabrutideg (BGB-16673), an orally bioavailable Bruton's tyrosine kinase (BTK)-targeted chimeric degradation activation compound (CDAC/PROTAC), with BRUKINSA (zanubrutinib), an approved small-molecule covalent BTK inhibitor. Tacabrutideg degrades both wild-type and resistance-associated mutant BTK proteins (including C481S, T474I, and L528W variants), while zanubrutinib inhibits BTK by covalently binding to its Cys481 residue. This combination is designed to overcome resistance to covalent BTK inhibitors and achieve deeper, more durable clinical responses.
- Other names
- Tacabrutideg + BRUKINSA
02
Targets
BTK (Bruton tyrosine kinase)CRBN (Cereblon)EGFR (Epidermal growth factor receptor)ERBB2 (Erb-b2 receptor tyrosine kinase 2)ERKITK (Interleukin 2-inducible T-cell kinase)JAK3 (Janus kinase 3)
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