TGFβ has profound local immunosuppressive and immunoexclusion effects in the tumor microenvironment that are integrally involved in the failure of immune checkpoint inhibitors in some tumors. Preclinical data in a variety of models strongly support the study of AVID200 in patients with treatment-refractory advanced and metastatic malignancies as an approach to reducing immunosuppression/exclusion and increasing the activity of immune checkpoint inhibitors.
TGFβ inhibits local anti-tumor immunity in the tumor microenvironment (TME) and also promotes the epithelial to mesenchymal transition (EMT) that enhances the metastatic potential of tumor cells. Cancer-associated fibroblasts (CAFs) are a critical constituent of the TME. As is the case for fibrosis in other settings, these cells are myofibroblast-like, and respond to and are activated by tumor-derived TGFβ. CAFs play a critical role in promoting EMT resulting in increased tumor cell migration and invasion as well as maintaining the TME to support tumor cell survival. The immunosuppressive role of TGFβ in the TME has been clearly demonstrated with the activation of CAFs being an important mechanism underlying immune cell exclusion. Exclusion of immune cells from tumors and local immunosuppression can both be reversed by AVID200 therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
A TGFβ receptor ectodomain-IgG Fc fusion protein inhibitor of TGFβ
START Midwest Clinic
Grand Rapids, Michigan, United States
MD Anderson Cancer Center
Houston, Texas, United States
Princess Margaret Cancer Centre
Toronto, Canada
Incidence of Treatment-Emergent Adverse Events
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, for up to 24 months
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