BackFelmetatug vedotin (PF-08046048, SGN-B7H4V)
Felmetatug vedotin is an investigational compound. Its safety and efficacy have not been established.
Overview + Rationale
- Felmetatug vedotin (PF-08046048; SGN-B7H4V) 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
Felmetatug vedotin (PF-08046048; SGN-B7H4V) is thought to induce tumor cell death through:
- Preferential release of MMAE within target cells and subsequent apoptosis1
- Bystander effect13
- Antibody-dependent cellular cytotoxicity1
- Antibody-dependent cellular phagocytosis1
- Induction of immunogenic cell death14,15
Stage of Development
Advanced Solid Tumors
Phase 1 Monotherapy
HR+/HER2- Metastatic Breast Cancer
Phase 1 Monotherapy