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.
Subjects must have had at least one prior treatment with systemic therapy for advanced and unresectable, or metastatic disease OR is intolerant to, has refused or for whom there are no standard therapies that impart significant clinical benefit in the opinion of the treating investigator.
An Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 1 for phase 1B. An ECOG Performance Status less than or equal to 2 for phase 2.
Subjects must not have more than one malignancy at the time of enrollment
Adult subjects ≥ eighteen years of age
Subjects with known MSI-H or dMMR tumor status
Subjects with severe uncontrolled hypertension as defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg
Subjects who have had prior treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors
Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 160 days after the last dose of study drug
University of Florida
Lead sponsor
Genentech, Inc.
Collaborator
Aveo Oncology Pharmaceuticals
Collaborator