FDA approves new adjuvant treatment option for ccRCC patients with recurrence risk

The U.S. Food and Drug Administration (FDA) has approved pembrolizumab, an immunotherapy, plus belzutifan, a HIF-2α inhibitor, as adjuvant treatment for adult patients with renal cell carcinoma with a clear cell component (ccRCC) at intermediate-high or high risk of recurrence following nephrectomy, with or without resection of metastatic lesions. The approval is based on results from the phase 3 LITESPARK-022 trial, led by Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute.

"This approval establishes this combination of pembrolizumab and belzutifan as a new adjuvant option for patients with ccRCC at increased risk of recurrence," said Choueiri. "Because surgery alone is not enough for many patients, a meaningful proportion will relapse, often with metastatic disease. This combination provides a more effective strategy to reduce the likelihood of the cancer returning than with pembrolizumab alone."

This is the first approval for belzutifan in earlier-stage ccRCC and the first approval for a PD-1 and HIF-2α inhibitor combination regimen. The FDA also approved the subcutaneous combination of pembrolizumab and berahyaluronidase alfa-pmph plus belzutifan.

The phase 3 LITESPARK-022 study, presented by Choueiri at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium, included 1,841 participants with ccRCC. Participating patients underwent surgery to remove the tumor and had no signs of cancer but had an elevated risk of recurrence. Patients were randomized to receive either pembrolizumab plus belzutifan after surgery or pembrolizumab plus placebo after surgery. 

With a median follow-up of 28.4 months, the combination of pembrolizumab plus belzutifan resulted in a 28% decrease in risk of recurrence, metastasis or death. About 81% of participants who took the two-drug regimen were cancer-free after an estimated 24 months, compared to 74% of those who received the standard of care regimen of pembrolizumab plus placebo. Side effects were consistent with data from previously reported studies.

The HIF-2α inhibitor belzutifan helps to reduce risk of progression by blocking HIF-2α, which is overabundant in ccRCC cells and drives cancer growth. Dana-Farber's William G. Kaelin, Jr., MD, was awarded a Nobel Prize in Physiology or Medicine in 2019 for the science behind the development of belzutifan.

Renal cell carcinoma (RCC) is the most common type of kidney cancer, with about nine out of 10 kidney cancer diagnoses being RCC. In 2022, there were about 435,000 new cases of kidney cancer diagnosed and approximately 156,000 deaths from the disease worldwide. Clear cell renal cell carcinoma, which accounts for 75% of RCC diagnoses, is the most common subtype. About 30% of patients with ccRCC experience disease recurrence within five years following nephrectomy.