Felmetatug vedotin (B7-H4-directed Antibody Drug Conjugate)
Felmetatug vedotin is an investigational compound. Its safety and efficacy have not been established.
Overview + Rationale
- Felmetatug vedotin is an investigational antibody-drug conjugate (ADC) comprising 3 components: a monoclonal antibody directed to B7-H4, a microtubule-disrupting agent MMAE (monomethyl auristatin E), and a protease-cleavable mc-vc (maleimidocaproyl-valine-citrulline) linker that covalently attaches MMAE to the antibody, which enables preferential release of MMAE within target cells1
- B7-H4 is a member of the B7 family of immune checkpoint ligands and has been shown to negatively regulate T-cell function2,3
- B7-H4 binds to an unknown receptor on T cells and inhibits T-cell proliferation and cytokine production2-4
- B7-H4 expression is elevated across a broad range of solid tumors, including ovarian cancer, breast cancer, endometrial carcinoma, cholangiocarcinoma and gallbladder carcinoma, and squamous non-small cell lung cancer tumors5-12
- B7-H4 expression is limited in normal tissue, specifically immune cells, making it an ideal molecular target for ADCs2,3
- Felmetatug vedotin may have the potential to drive antitumor T-cell responses through depletion of immune-inhibitory B7-H4-expressing tumor cells1-3
Mechanism of Action
PF-08046048; SGN-B7H4V is thought to induce tumor cell death through:
• Preferential release of MMAE within target cells and subsequent apoptosis 1
• Bystander effect 13 • Antibody-dependent cellular cytotoxicity 1
• Antibody-dependent cellular phagocytosis 1
• Induction of immunogenic cell death 14,15
![](/sites/default/files/2024-05/USM-PPL-2021-0009_SGN-B7H4V_FA_4x3_full.jpg)
Stage of Development
Advanced Solid Tumors
Phase 1 Monotherapy
HR+/HER2- Metastatic Breast Cancer
Phase 1 Monotherapy