The U.S. Food and Drug Administration (FDA) has approved the immunotherapy pembrolizumab and the HIF-2α inhibitor velzutifan as adjuvant therapy for adult patients with clear cell renal cell carcinoma (ccRCC) who are at intermediate to high risk of recurrence after nephrectomy, with or without resection of metastatic disease. This approval is based on results from the Phase 3 LITESPARK-022 trial led by Toni Choeiri, MD, director of the Lanc Genitourinary Oncology Center at Dana-Farber Cancer Institute.
This approval establishes this combination of pembrolizumab and belzutifan as a new adjuvant treatment option for patients with ccRCC who are at high risk of recurrence. Surgery alone is not sufficient for many patients, and recurrence occurs at a significant rate, often with metastatic disease. This combination provides a more effective strategy to reduce the chance of cancer recurrence than pembrolizumab alone. ”
Dr. Toni Choueiri, Director, Rank Genitourinary Oncology Center, Dana-Farber Cancer Institute
This is the first approval of belzutifan in early-stage ccRCC and the first approval of a PD-1 and HIF-2α inhibitor combination therapy. The FDA also approved subcutaneous combination therapy of pembrolizumab and verahyaluronidase alpha-pmph and velzutifan.
The phase 3 LITESPARK-022 trial, presented by Choueiri at the 2026 American Society of Clinical Oncology Urinary Tract Cancer Symposium, included 1,841 participants with ccRCC. The participating patients had surgery to remove the tumor and had no signs of cancer, but were at high risk of recurrence. Patients were randomly assigned to receive postoperative pembrolizumab and belzutifan or postoperative pembrolizumab and placebo.
With a median follow-up of 28.4 months, the combination of pembrolizumab and belzutifan reduced the risk of recurrence, metastasis, or death by 28%. About 81% of participants who received the two-drug combination were cancer-free after an estimated 24 months, compared with 74% of participants who received standard-of-care therapy of pembrolizumab and a placebo. Side effects were consistent with data from previously reported studies.
The HIF-2α inhibitor Belzutifan reduces the risk of progression by blocking HIF-2α, which is present in excess in ccRCC cells and promotes cancer growth. Dana-Farber’s William G. Kaelin, Jr., MD, won the 2019 Nobel Prize in Physiology or Medicine for the science behind the development of Belzutifan.
Renal cell carcinoma (RCC) is the most common type of kidney cancer, and approximately 9 out of 10 people diagnosed with kidney cancer have RCC. In 2022, approximately 435,000 people will be newly diagnosed with kidney cancer and approximately 156,000 people will die from kidney cancer worldwide. Clear cell renal cell carcinoma accounts for 75% of RCC diagnoses and is the most common subtype. Approximately 30% of ccRCC patients experience recurrence within 5 years after nephrectomy.
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Dana-Farber Cancer Institute
