BackPD-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 PD-L1 (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/PD-L1 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
- The proposed MOAs of PDL1V reflect the hallmarks of vedotin-based ADCs: MMAE-induced cytotoxicity against PD-L1-expressing tumor cells, immunogenic cell death (ICD), and bystander effect 1
- The PDL1V antibody has been designed to enable targeting of PD-L1 with an ADC through engineering for potential of increased internalization and payload delivery1
Mechanism of Action
Stage of Development
This information is current as of February 4th 2025.
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 January 16, 2025.