Chicago’s Rush University Medical Center is recruiting patients with advanced renal cell carcinoma for a Phase 2 trial to evaluate whether Opdivo (nivolumab) combined with other investigational immunotherapy drugs is more effective than the currently used Opdivo-Yervoy (ipilimimab) combo therapy.
The study is expected to enroll about 650 adults whose renal cell carcinoma has spread, with at least one detected metastasis.
“Ten years ago, patients with advanced kidney cancer had few options and little hope, Dr. Timothy Kuzel, Rush’s chief of hematology, oncology and cell therapy and the clinical trial’s principal investigator, said in a press release. “But just in the last few years, new drug combinations have resulted in long-lasting remission for many, but more investigations need to be done to help those kidney cancer patients who have not yet benefitted.”
Opdivo and Yervoy — both manufactured by Bristol Myers Squibb — are monoclonal antibodies designed to boost the ability of immune cells to detect and destroy cancer cells. Combining these two checkpoint inhibitors is now potentially the most effective treatment option, with proven increases in survival rates and quality of life. Yet only a few respond to treatment.
“Nivolumab [Opdivo] removes the brakes that cancer cells have put on the immune system, while ipilimumab [Yervoy] steps on the gas and accelerates the production of T cells,” Kuzel said. “But we know this combination doesn’t work for everyone and that there are several other potential targets that activate the immune system’s tumor-fighting capabilities. Thus we’re excited about the new study to learn whether a series of novel immunotherapy combinations — immunotherapy cocktails — can be integrated into kidney cancer treatments.”
Rush will conduct the nationwide, multicenter FRACTION-RCC study (NCT02996110) to find ways to boost the number of patients responding to the emergent immunotherapies. In particular, FRACTION-RCC will assess if combining Opdivo with a Lag-3 inhibitor — another immune checkpoint inhibitor — is better than the Opdivo-Yervoy combo.
The study’s primary goals include objective response rate, duration of response and progression-free survival. Secondary endpoints are safety and tolerability. This clinical trial may also provide new prognostic tools, such as immune system biomarkers, that can help oncologists predicting patients responses to therapies, allowing a more suitable and individualized anti-cancer approach.
“Most cancer biomarkers, such as specific genetic mutations or proteins, are binary — they are either present or not,” said Kuzel. “But as we better measure and understand the intricate ways in which our immune system and cancer cells do battle, the quicker we can develop new ways for more people to activate their immune systems to win that battle.”