Experimental drug combination shows early effectiveness in advanced kidney cancer

PHOENIX — An experimental drug combination may help overcome treatment resistance in advanced kidney cancer, according to early results from a first-in-human clinical trial led by Mayo Clinic researchers.

The study evaluated the investigational drug darlifarnib in combination with the targeted therapy cabozantinib, a standard treatment for clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer. Among patients whose disease had progressed despite prior treatment, 44% responded to the combination therapy, while disease control was achieved in 94% of participants.

"These early findings are encouraging, as more effective treatments are urgently needed for patients with advanced disease," says Yousef Zakharia, M.D., principal investigator of the study and a medical oncologist at Mayo Clinic in Arizona. He presented the findings at the 2026 International Kidney Cancer Symposium: Europe in Paris.

ccRCC accounts for most kidney cancer cases in adults, and many patients eventually experience disease progression despite treatment.

In the phase 1a/b study, researchers evaluated 18 patients who had previously received cabozantinib. About half had undergone at least three prior therapies.

"For many patients, the benefit of cabozantinib can be temporary. Tumors may develop resistance and activate alternative pathways that allow the cancer to continue growing," Dr. Zakharia says.

Researchers investigated whether adding darlifarnib, a next-generation targeted therapy designed to inhibit cancer growth signaling pathways, could help overcome treatment resistance.

The combination produced tumor shrinkage in 7 of 16 evaluable patients, corresponding to an overall response rate of 44%. Disease control, defined as either tumor stability or shrinkage, was achieved in 15 of 16 patients (94%).

"These findings require validation in a larger clinical trial to confirm the efficacy observed thus far; however, the early signal is intriguing," says Dr. Zakharia. "This study represents an important step forward and provides insight into how treatment resistance might be overcome."

The multicenter, international trial will further evaluate the benefit of the combination in a larger group.

For a complete list of trial and funding information, review the study.

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