Roger Li, MD, Provides In-Depth Description of CG0070 Mechanism of Action in Bladder Cancer

Roger Li, MD, spoke about the mechanism of action of CG0070 used in combination with pembrolizumab to treat patients with non–muscle invasive bladder cancer who were unresponsive to bacillus Calmette-Guerin.

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Roger Li, MD, a genitourinary oncologist from Moffitt Cancer Center, spoke with CancerNetwork® about the phase 2 CORE1 trial (NCT04452591) which investigated CG0070, an oncolytic vaccine, plus pembrolizumab (Keytruda) for patients with non–muscle invasive bladder cancer who were unresponsive to bacillus Calmette-Guerin (BCG), an intravesical immunotherapy. He spoke about the mechanism of action of CG0070, which has previously shown a benefit for those with BCG-refractory bladder cancer.

Transcript:

The oncolytic virus is an adenovirus backbone, Ad5 [adenovirus type 5], that detects cancer cells with a defective RB protein. Because of the defective RB protein, there is an increase in the E2 factor in the cells, which binds to the promoters of the virus and elicits the viral replication. In addition to that, the viral backbone also contains a GM-CSF transgene. It secretes GM-CSF, and the thought is it would attract antigen-presenting cells to the tumor microenvironment.

It has been tested in bladder cancer in the past, specifically for patients who have been refractory to BCG with non–muscle invasive bladder cancer. In those clinical trials, it has been safe and efficacious with about a 1-year complete response rate of 26% in those patients. The reason why we wanted to combine it with an immune checkpoint [inhibitor] is we theorize that there is a synergism between the mechanism of action of the oncolytic virus and immune checkpoint [inhibitors]. The virus can attract the immune cells to the tumor microenvironment, they act against the cancer cells, attack them, [the cells] get exhausted, and in turn, can be reinvigorated by the immune checkpoint blockade. Indeed, that’s what we’re seeing as the preliminary results of our clinical trial.

Reference

Li R, Steinberg GD, Lamm D, et al. CORE1: Phase 2, single-arm study of CG0070 combined with pembrolizumab in patients with nonmuscle-invasive bladder cancer (NMIBC) unresponsive to bacillus Calmette-Guerin (BCG). J Clin Oncol. 2022; 40(suppl 16):4597. Doi: 10.1200/JCO.2022.40.16_suppl.4597