The U.S. Food and Drug Administration has approved pembrolizumab, an immunotherapy, combined with belzutifan, a HIF-2α inhibitor, as adjuvant treatment for adult patients with renal cell carcinoma with a clear cell component who are at intermediate-high or high risk of recurrence following nephrectomy, with or without resection of metastatic lesions, according to a June 12 announcement.
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 marks the first approval for belzutifan in earlier-stage clear cell renal cell carcinoma (ccRCC) and also represents the first FDA approval for a PD-1 and HIF-2α inhibitor combination regimen. The FDA additionally approved the subcutaneous combination of pembrolizumab and berahyaluronidase alfa-pmph plus belzutifan.
The phase 3 LITESPARK-022 study included 1,841 participants who had undergone surgery to remove their tumor but remained at elevated risk of recurrence. Patients were randomized to receive either pembrolizumab plus belzutifan or pembrolizumab plus placebo after surgery. With a median follow-up period of 28.4 months, results showed that those receiving both drugs experienced a 28% decrease in risk of recurrence, metastasis, or death compared to those receiving standard care. Approximately 81% of participants on the two-drug regimen were cancer-free after an estimated 24 months versus 74% in the control group; side effects were consistent with previous studies.
Belzutifan works by blocking HIF-2α—a protein overabundant in ccRCC cells—which helps reduce progression risks by impeding cancer growth pathways identified through research recognized by William G. Kaelin Jr., MD’s Nobel Prize in Physiology or Medicine in 2019.
Renal cell carcinoma is reported as the most common type of kidney cancer worldwide; about nine out of ten kidney cancers are RCCs and clear cell subtype accounts for roughly three quarters of these cases. In recent years there have been approximately 435,000 new diagnoses annually along with around 156,000 deaths globally attributed to kidney cancer.
