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zilovertamab vedotin + nemtabrutinib
- Development stage
- Unknown
- Lead developer
- Merck
- Modality
- Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics
- Administration
- Intravenous, Oral
01
Overview
Zilovertamab vedotin + nemtabrutinib is an investigational combination therapy consisting of two targeted agents under clinical development—zilovertamab vedotin and nemtabrutinib—primarily for hematologic malignancies such as diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). **Zilovertamab vedotin** is an antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1) expressed on malignant B cells. It consists of a monoclonal antibody specific for ROR1, a protease-cleavable linker, and the cytotoxic payload monomethyl auristatin E (MMAE), which disrupts microtubule polymerization, leading to cell death. **Nemtabrutinib** is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK), a critical kinase in B-cell receptor signaling, including in BTK inhibitor–resistant cells. The combination aims to disrupt complementary survival pathways in malignant B-cells, leveraging the targeted cytotoxicity of the ADC and downstream inhibition of B-cell signaling. Both agents are being developed by Merck for B-cell malignancies; combination trials exist or are planned for high-risk and relapsed/refractory lymphoma and other lymphoid neoplasms[1][2][3][4][5][6][7].
- Other names
- zilovertamab vedotin + nemtabrutinib
02
Targets
ROR1 (Receptor tyrosine kinase-like orphan receptor 1)TUBB (Tubulin (alpha and beta subunits))BTK (Bruton tyrosine kinase)
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