Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Rare Diseases

Prostatic Neoplasms

Adenocarcinoma

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cholangiocarcinoma

Urinary Bladder Neoplasms

Vulvar Neoplasms

Neuroendocrine Tumors

Respiratory Tract Infections

Carcinoma, Neuroendocrine

Sarcoma

Bile Duct Neoplasms

Gallbladder Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Connective and Soft Tissue

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Gastrointestinal Diseases

Vulvar Diseases

Gallbladder Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Bile Duct Cancer

Neuroendocrine Tumor

Gallbladder Cancer

Soft Tissue Sarcoma

Vulvar Cancer

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Tivozanib

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

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.

Priya Gurjar

Brandie Feeney

Jonathan Chatzkel, MD

Brian Ramnaraign, MD

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.

Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types

To determine the best overall response rate (ORR) of atezolizumab plus tivozanib in subjects with immunologically cold tumors

To determine the progression free survival (PFS) of subjects with immunologically cold tumors receiving atezolizumab plus tivozanib

To determine the overall survival (OS) of subjects with immunologically cold tumors receiving atezolizumab plus tivozanib.

To determine the disease control rate (DCR) of subjects with immunologically cold tumors receiving atezolizumab plus tivozanib. DCR is defined as percentage of subjects who achieve complete response, partial response and stable disease during the course of study using RECIST v1.1 criteria.

Genentech, Inc.

Aveo Oncology Pharmaceuticals

University of Florida

Spots Global Cancer Trial Database for immunologically cold tumors