NCT03834662

A Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients Malignancies

A Phase 1 Cohort Dose-Escalation Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients With Advanced or Metastatic Solid Tumor Malignancies

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Bristol-Myers Squibb · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Malignant Solid Tumor

Interventions

Type	Name	Description
DRUG	AVID200	A TGFβ receptor ectodomain-IgG Fc fusion protein inhibitor of TGFβ

Timeline

• Start date: 2019-01-07
• Primary completion: 2020-02-19
• Completion: 2020-02-19
• First posted: 2019-02-08
• Last updated: 2024-11-19

Locations

3 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study