SGN-PDL1V is an investigational vedotin antibody-drug conjugate (ADC) directed to the T cell checkpoint ligand, PD-(L)1 being developed by Seagen.[1][2]
PD-(L)1 is a target with limited normal tissue expression and clinically validated expression across a variety of malignancies, including non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinomas (HNSCC). SGN-PDL1V is engineered for efficient delivery of the therapeutic payload, monomethyl auristatin E (MMAE), and is proposed to have distinct mechanisms of action from other PD-(L)1-directed therapeutics, including direct cytotoxicity against PD-(L)1-expressing cells, bystander killing, and immunogenic cell death.
Robust antitumor activity
SGN-PDL1V demonstrates robust antitumor activity in xenograft models, including in tumors with low, heterogeneous PD-(L)1 expression, supporting the potential to treat patients across a wide range of PD-(L)1 expression levels.
For example, in pre-clinical studies, SGN-PDL1V demonstrated in vitro, internalization and potent cytotoxic activity against PD-L1 expressing tumor cells. Furthermore, in vivo, SGN-PDL1V achieved tumor regressions in multiple tumor xenograft models at doses as low as 1 mg/kg when dosed weekly for a total of three doses.[2]
Immunocompromised mice
This activity was observed in immunocompromised mice, which lack responses to PD-1/PD-L1 inhibition. The investigators noted that this activity was observed even in xenograft models with low, heterogeneous PD-L1 expression. Based on this observation, they believe that this supports the possibility to treat patients across a wide range of PD-L1 expression levels with SGN-PDL1V. The investigators also noted that SGN-PDL1V exhibited the potential to inhibit the PD-1/PD-L1 checkpoint in vitro and in vivo. The tolerability and safety profile of SGN-PDL1V were assessed in a non-human primate study and found to be comparable to other approved ADCs with a similar (vedotin) payload and linker chemistry.[2]
Reference
[1] ADC Review | Drugmap [Link]
[2] , et al 783 SGN-PDL1V, a novel, investigational PD-L1-directed antibody-drug conjugate for the treatment of solid tumors
Last updated on January 19, 2022
