Dr. Ramnaraign on the Investigation of Atezolizumab Plus Tivozanib in CRPC

Brian Ramnaraign, MD, assistant professor of medicine, Division of Hematology and Oncology, University of Florida College of Medicine, discusses the investigation of atezolizumab (Tecentriq) with tivozanib (Fotivda) in castrate-resistant prostate cancer (CRPC).

The ongoing phase 1b/2 IMMCO-1 trial (NCT05000294) is examining the combination of atezolizumab with tivozanib in patients with unresectable or metastatic immunologically cold tumors, including CRPC previously treated with an androgen receptor inhibitor or cytotoxic chemotherapy in the advanced or metastatic setting, bile duct or gallbladder cancer, select hormone receptor–negative/HER2-positive breast cancers, ovarian cancer, pancreatic adenocarcinoma, soft tissue sarcoma, or vulvar cancer, who have received at least one prior systemic therapy in this setting.

CRPC is an immunologically cold tumor, and historical data have shown that patients with CRCP experienced an overall response rate of only 5% when treated with the PD-L1 inhibitor, pembrolizumab (Keytruda). Since VEGF inhibitor may enhance the effect of PD-(L)1–directed therapy, investigators are examining the use of the PD-L1 inhibitor atezolizumab in combination with the VEGF TKI tivozanib.

At the 2023 Genitourinary Cancers Symposium, investigators presented information on the IMMCO-1 study, which is trial in progress. Checkpoint inhibition has improved cancer outcomes in a variety of cancers, such as bladder cancer, kidney cancer, and lung cancer, Ramnaraign notes. However, checkpoint inhibitors don't work for all cancers, including many gastrointestinal cancers, Ramnaraign adds.

Investigators hypothesized that an immunologically cold tumor could be turned into a hot tumor by modulating the tumor microenvironment, recruiting a cytotoxic T lymphocytes, and changing the vascular permeability of tumors through the use of a VEGF TKI, Ramnaraign continues.

If investigators observe responses in patients enrolled in the basket study, the investigation could lead to a larger phase 2 clinical trial, Ramnaraign explains. Additionally, this trial could help patients by providing them with an additional line of therapy and allowing them to receive a checkpoint inhibitor, which is known to be a safe and efficacious option many patients with metastatic cancers, Ramnaraign concludes.