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.

PD-L1-directed Antibody Drug Conjugate

Geo Regions

PD-L1-directed Antibody Drug Conjugate

PF-08046054, SGN-PDL1V is an investigational compound. Its safety and efficacy have not been established

Overview + Rationale

  • PF-08046054, SGN-PDL1V is an investigational antibody-drug conjugate (ADC) that contains 3 components: a monoclonal antibody directed to PDL1 (programmed death ligand 1), 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 
  • PD-L1 is a cell-surface protein primarily known for its role in the PD-1/PDL1 immune checkpoint, which inhibits T-cell activation2-4 
  • Expression of PD-L1 in tumors can signal through PD-1 on T cells to inhibit T-cell effector function2 
  • PD-L1 expression is elevated in multiple solid tumors, including head and neck squamous cell carcinoma, non-small-cell lung cancer, melanoma, triple-negative breast cancer, urothelial cancer, cervical cancer, gastric cancer, ovarian cancer, and esophageal cancer1,2-17 
  • The elevated expression of PD-L1 in solid tumors relative to normal tissue makes it an ideal molecular target for ADCs1 
  • PF-08046054; SGN-PDL1V may have the potential to drive antitumor T-cell responses through inhibition of the PD-1/PD-L1 immune checkpoint1

Mechanism of Action

PF-08046055; SGN-PDL1V is thought to induce tumor cell death through: 

• Preferential release of monomethyl auristatin E within target cells and subsequent apoptosis 

• Bystander effect 

• Induction of immunogenic cell death 

To limit potential immune-related toxicity, the mAb used in PF-08046055; SGN-PDL1V is engineered to potentially eliminate complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis.

Stage of Development

Small icon representing early solid tumors
Advanced Solid Tumors
Phase 1 Monotherapy and Combination

REFERENCES: 1. Kwan B. SITC 2021: Poster 783; 2. Chen DS. Immunology. 2013: 1-10; 3. Pardoll DM. Nat Rev Cancer. 2012: 252-64; 4. O'Malley D. Mod Pathol. 2019: 929-42; 5. Cha JH. Mol Cell. 2019: 359-70; 6. Balar A. Lancet Oncol. 2017: 1483-92; 7. Burtness B. Lancet. 2019: 1915- 28; 8. Chung HC. J Clin Oncol. 2019: 1470-8; 9. Fuchs CS. JAMA Oncol. 2018: e180013; 10. Herbst R. Lancet. 2016: 1540-50; 11. Mok T. Lancet. 2019: 1819-30; 12. Reck M. N Engl J Med. 2016: 1823-33; 13. Robert C. N Engl J Med. 2015: 320-30; 14. Schmid P. N Engl J Med. 2020: 810-21; 15. Shah M. JAMA Oncol. 2019: 546-50; 16. Shitara K. Lancet. 2018: 123-33; 17. Varga A. Gyn Oncol. 2019: 243-50; 18/ NCT05208762. https://clinicaltrials.gov/study/NCT05208762 Accessed February 25, 2024.