Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types
Status:
Recruiting
Trial end date:
2024-06-01
Target enrollment:
Participant gender:
Summary
Checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction
between PD-1 and PD-L1 induces immune tolerance, and the inhibition of this interaction is an
effective treatment strategy for numerous malignancies.
Despite its demonstrated potential, immunotherapy is not currently thought to be an effective
intervention in the treatment of several immunologically "cold" tumors such as prostate
cancer, biliary tract cancers, soft tissue sarcomas, well-differentiated neuroendocrine
tumors, microsatellite stable colorectal cancer, pancreatic cancer, and non-triple negative
breast cancer.
Vascular endothelial growth factor (VEGF) is thought to play a key role in modulating the
anti-tumor immune response. Vascular endothelial growth factor (VEGF) is secreted by tumors
and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in
turn leads to the development of an abnormal vasculature with excessive permeability and poor
blood flow, limiting immune surveillance. In addition, VEGF inhibits dendritic cell
differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Vascular
endothelial growth factor (VEGF). VEGF tyrosine kinase inhibitors (TKIs) VEGF-TKIs are
currently utilized in the treatment of a variety of malignancies and are widely utilized in
combination with checkpoint blockade in the treatment of clear cell kidney cancer.
Through the inhibition of VEGF, it may be possible to potentiate the effect of immune
checkpoint blockade even in tumors which have traditionally been thought to be unresponsive
to immunotherapy. This study aims to evaluate the combination of the immune checkpoint
inhibitor atezolizumab and the VEGF-TKI tivozanib in a variety of tumors which have a low
response rate to checkpoint inhibitor therapy alone.