Novel Immunotherapy Trials May Drive Progress in Kidney Cancer Field

Although prior work has demonstrated the efficacy of stimulating the immune system to treat patients with kidney cancer, the field must “do better” to continue improving outcomes across this population, according to Eric Jonasch, MD.

In a collaboration with KidneyCAN, CancerNetwork^® spoke with Jonasch about notable immunotherapy-based studies that the Kidney Cancer Research Consortium has organized to potentially improve the treatment of those with kidney cancer. These trials have assessed how the addition of novel agents may enhance the efficacy of standard options such as immune checkpoint inhibitors and anti–CTLA-4 therapies in this population.

For example, Jonasch highlighted a phase 1b/2 trial (NCT05501054) evaluating the adenosine A2a receptor inhibitor ciforadenant (CPI-444) in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) for patients with advanced renal cell carcinoma (RCC).¹ Additionally, he described a phase 2 study (NCT06284564) assessing how immunotherapy strategies may be bolstered by adding evolocumab (Repatha) to nivolumab for those with metastatic RCC.²

Jonasch is a professor in the Department of Genitourinary Medical Oncology of the Division of Cancer Medicine and the director of the von Hippel Lindau Center at The University of Texas MD Anderson Cancer Center in Houston, Texas.

KidneyCAN is a nonprofit organization with a mission to accelerate cures for kidney cancer through education, advocacy, and research funding. Learn more about KidneyCAN’s mission and work here.

Transcript:

We know that the immune system is important in the treatment of patients with renal cell carcinoma, and stimulating the immune system is super important. Having said that, we have demonstrated that we have achieved success with that kind of a strategy. But the success is not universal, and we need to do better.

A lot of the trials that we have running or have now completed are taking a backbone of immunotherapy that we use. These are checkpoint-blocking antibodies—for example, nivolumab or pembrolizumab [Keytruda]—or CTLA-4–blocking agents like ipilimumab, and then adding agents that may be tweaking the way the immune cells are reacting to the tumor cells. We know, for example, that there are sometimes deficiencies in the way the immune cells react, because the tumors are throwing things at them that don’t make them work as well.

For example, there was a study that was led by Kathryn E. Beckermann, MD, PhD, using an A2A receptor inhibitor, which basically blocks the ill effects of adenosine on the immune cells. It’s a trial where we used a standard backbone of ipilimumab/nivolumab and added this A2A receptor inhibitor called ciforadenant. That’s an example.

Another study that’s being led by Tian Zhang, MD, at UT Southwestern is looking at the addition of a cholesterol-modifying agent called evolocumab, which changes how some of the proteins that make the cancer cells visible to the immune cells are processed on the surface of the cell. We’re looking at a combination of evolocumab plus nivolumab, which is a PD-1–blocking agent.

These are just 2 examples of trials that are being led by investigators in the consortium, which are helping us to move things forward.

References

1. Beckermann K, Rini B, Haas N, George D, Jonasch E. Phase 1b/2 trial of ipilimumab, nivolumab, and ciforadenant (INC) (adenosine A2a receptor antagonist) in first-line advanced renal cell carcinoma. Oncologist. 2023;28(suppl 1):S13–4. doi:10.1093/oncolo/oyad216.022.
2. A phase II study bolstering outcomes by optimizing immunotherapy strategies with evolocumab and nivolumab in patients with metastatic renal cell carcinoma (BOOST-RCC). ClinicalTrials.gov. Updated November 13, 2024. Accessed January 8, 2025. https://tinyurl.com/yn634c4v