FDA Approves Adjuvant Belzutifan/Pembrolizumab in Clear Cell RCC Post Nephrectomy

Adjuvant belzutifan (Welireg) plus pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) has been approved by the FDA for patients with clear cell renal cell carcinoma (ccRCC) who have an intermediate or high risk of recurrence after nephrectomy, or after nephrectomy and resection of metastatic lesions, according to a press release from the FDA.¹

Data from the phase 3 LITESPARK-022 trial (NCT05239728), which were previously presented at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, led to the approval.²

At the time of the presentation, the disease-free survival (DFS) was not reached (NR; 95% CI, 36.9 months-NR) in the belzutifan arm vs NR (95% CI, NR-NR) in the pembrolizumab alone arm (HR, 0.72; 95% CI, 0.59-0.87; P = .0003). Additionally, the 12-month DFS rates were 91.9% vs 85.2%, respectively; the 24-month rates were 80.7% vs 73.7%, and the 30-month rates were 75.8% vs 68.6%.

The median overall survival (OS) was NR in both arms, and statistical significance was not met (HR, 0.78; 95% CI, 0.51-1.19; P = .1220). The 12-month OS rates were 98.3% vs 98.6%, respectively; the 24-month rates were 96.2% vs 95.7%, and the 30-month rates were 95.6% vs 93.8%.

In the press release from the FDA, the recommended dose for belzutifan was 120 mg orally once daily plus pembrolizumab or pembrolizumab and berahyaluronidase-pmph alfa given until disease recurrence, unacceptable toxicity, or up to 54 weeks.

For pembrolizumab, the recommended dose was 200 mg intravenously every 3 weeks or 400 mg every 6 weeks. This was given in combination with belzutifan until disease recurrence, unacceptable toxicity, or for up to 12 months. The recommended dose for pembrolizumab and berahyaluronidase alfa-pmph was 395 mg/4800 units subcutaneously every 3 weeks or 790 mg/9600 units every 6 weeks in combination plus belzutifan at 120 mg orally once a day until disease recurrence, unacceptable toxicity, or for up to 12 months.

References

1. FDA approves belzutifan with pembrolizumab for adjuvant treatment of renal cell carcinoma. News release. June 12, 2026. Accessed June 12, 2026. https://tinyurl.com/mpa3uh62
2. Choueiri TK, Motzer RJ, Karam JA, et al. Adjuvant pembrolizumab plus belzutifan versus pembrolizumab for clear cell renal cell carcinoma (ccRCC): the randomized phase 3 LITESPARK-022 study. J Clin Oncol. 2026;44(suppl 7):LBA418. doi:10.1200/JCO.2026.44.7_suppl.LBA418