NCT05000294

Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types

• Status: Suspended
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Bile Duct Cancer
• Gall Bladder Cancer
• Breast Cancer
• Neuroendocrine Tumors
• Ovarian Cancer
• Pancreatic Adenocarcinoma
• Soft Tissue Sarcoma
• Vulvar Cancer
• Prostate Cancer

Interventions

Type	Name	Description
DRUG	Atezolizumab	Subjects on both the phase Ib and phase II portions of this study will receive 1680 mg intravenously of atezolizumab on Day 1 of each 28 day cycle.
DRUG	Tivozanib	Subjects in both the phase Ib and phase II portions of the study will take tivozanib orally once daily on Days 1-21 of each 28 day cycle. Subjects on the phase Ib will be assigned to receive either 1.34 mg/day (Dose level 0) or 0.89 mg/day (Dose level -1). Subjects in the phase II portion of the study will receive 0.89 mg/day.

Timeline

• Start date: 2021-12-07
• Primary completion: 2026-12-01
• Completion: 2027-06-01
• First posted: 2021-08-11
• Last updated: 2026-02-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study