The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Felmetatug vedotin (B7-H4-directed Antibody Drug Conjugate)

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Felmetatug vedotin (B7-H4-directed Antibody Drug Conjugate)

Felmetatug vedotin is an investigational compound. Its safety and efficacy have not been established.

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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

Stage of Development

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Advanced Solid Tumors
Phase 1 Monotherapy
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Triple-Negative or HR+/HER2- Metastatic Breast Cancer
Phase 1 Monotherapy

REFERENCES:  1. Gray E. SITC 2021: EP854; 2. Sica GL. Immunity. 2003: 849-61; 3. Zang X. Proc Natl Acad Sci. 2003: 10388-92; 4. Dangaj D. Cancer Res. 2013: 4820-29; 5, Leong SR. Mol Pharm. 2015: 1717-29; 6. Liang L. Hum Pathol. 2016: 1-6; 7. Liu CL. Eur Rev Med Pharmacol Sci. 2016: 4466-73; 8. Zhao X. Oncol Rep. 2016: 419-27; 9. Bregar A. Gynecol Oncol. 2017: 446-52; 10. Schalper KA. Clin Cancer Res. 2017: 370-78; 11. Xie N. Cell Death Dis. 2017: 3205; 12. Altan M. NPJ Breast Cancer. 2018: 4:40; 13. Burton JK. AAPS J. 2019:12; 14. Gray E. AACR 2022: Poster 1261; 15. Ulrich M. SITC 2022: Poster 1190; 16. NCT05194072. https://clinicaltrials.gov/ct2/show/NCT05194072. Accessed July 23, 2024.