Dr. Subudhi Discusses Rationale for CheckMate-650 Study in Prostate Cancer

Sumit K. Subudhi, MD, PhD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the rationale for the CheckMate-650 study in metastatic castration-resistant prostate cancer (mCRPC).

As a monotherapy, checkpoint inhibitors have had very limited efficacy in prostate cancer. For example, use of the anti—PD-1 agent nivolumab (Opdivo) as a monotherapy had failed to demonstrate responses in a phase I trial, Subudhi says. There were also 2 phase III trials which investigated the use of the anti–CTLA-4 agent ipilimumab (Yervoy) as a monotherapy, and neither demonstrated an overall survival benefit. Because checkpoint inhibitors have shown efficacy in other cancer types, researchers from The University of Texas MD Anderson Cancer Center decided to explore the issue further.

In prostate cancer, when one looks at the tumor microenvironment prior to treatment, there are very few T cells present, unlike other cancers like lung cancer and melanoma, explains Subudhi. When you give 2 doses of anti—CTLA-4 therapy, you can drive T cells into the cancer. However, the tumor microenvironment of prostate cancer appears to upregulate other immune checkpoints, which prevents those activated T cells from eliminating the tumor. However, in preclinical trials, researchers combined anti–CTLA-4 and anti–PD-1 agents and saw impressive durable responses.

That led to the decision to launch the CheckMate-650 trial, which evaluated the use of the combination of nivolumab and ipilimumab in the treatment of patients with mCRPC. Results presented at the 2019 Genitourinary Cancers Symposium showed that a subset of patients derived benefit from the combination, with some patients achieving no detectable prostate-specific antigen levels.