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 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
Advanced Solid Tumors
Phase 1 Monotherapy and Combination