FDA grants priority review to adjuvant belzutifan plus pembrolizumab for ccRCC

The FDA has granted priority review to 2 supplemental applications seeking approval of belzutifan (Welireg) in combination with pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (KEYTRUDA QLEX) for the adjuvant treatment of adult patients with clear cell renal cell carcinoma (ccRCC) who are at an increased risk of recurrence following nephrectomy.¹

The agency has set a Prescription Drug User Fee Act (PDUFA), or target action date, of June 19, 2026.

The applications are supported by data from the phase 3 LITESPARK-022 study (NCT05239728), which were presented at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California by Toni K. Choueiri, MD.² Overall, the trial met its primary end point by showing that the addition of belzutifan to adjuvant pembrolizumab significantly improves disease-free survival (DFS) vs pembrolizumab alone (HR, 0.72; 95% CI, 0.59 to 0.87; P = .0003).

“Approximately 40% of patients with renal cell cancer may experience tumor growth after initial treatment. Results from LITESPARK-022 mark an important step forward for certain patients with renal cell cancer, showing a significant reduction in the risk of disease recurrence or death compared to pembrolizumab alone,” said Choueiri, director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg professor of medicine at Harvard Medical School, in a news release.¹ “The combination of pembrolizumab and belzutifan is the first ever regimen in the adjuvant setting for renal cell cancer to demonstrate an improvement in disease-free survival over pembrolizumab monotherapy, positioning this regimen to potentially reshape clinical practice.”

In total, the LITESPARK-022 trial enrolled 1841 patients. Participants were eligible for the study if they had histologically confirmed ccRCC with no prior systemic therapy, had undergone surgery 12 weeks or sooner prior to randomization, ECOG Performance Status of 0 or 1, and had 1 of either intermediate-high risk of recurrence, high risk of recurrence, or M1 no evidence of disease.

Those included in the study were randomly assigned 1:1 to either pembrolizumab 400 mg every 6 weeks for approximately 1 year (9 or fewer cycles) plus belzutifan 120 mg once daily for 54 weeks or less (921 patients), or to pembrolizumab 400 mg every 6 weeks for approximately 1 year (9 or fewer cycles) plus placebo once daily for 54 weeks or less (920 patients). The primary end point was DFS by investigator assessment, and OS was the key secondary end point. Safety was another secondary end point.

A total of 636 (69.5%) patients completed treatment in the belzutifan arm, and 649 (71.1%) patients completed treatment in the placebo arm.

At the median follow-up of 28.4 months, the median DFS had not been reached. The estimated 24-month DFS rate was 80.7% (95% CI, 77.7 to 83.2) for the belzutifan plus pembrolizumab arm and was 73.7% (95% CI, 70.6 to 76.6) for the pembrolizumab monotherapy arm. Examining DFS in subgroups such as age, sex, race, ECOG Performance Status, geographic region, PD-L1 status, risk category, and tumor grade, Choueiri reported at ASCO GU that most HRs were below 1.0.

Choueiri also shared interim OS results; the HR was 0.78 (95% CI, 0.51-1.19; P = .1220).

Regarding safety, grade 3 or higher adverse events (AEs) were reported in 52.1% of patients in the combination arm and 30.2% of patients in the pembrolizumab monotherapy arm. The most common treatment-emergent AEs were anemia (12.1% vs 0.5%), increased alanine aminotransferase (6.4% vs 2.0%) and hypoxia (4.6% vs 0%). The incidence of grade 5 treatment-emergent AEs was 1.1% in the combination arm vs 1.2% in the pembrolizumab monotherapy arm. The incidence of treatment-related AEs was also comparable between both study cohorts, with a rate of 0.3% in each.

Merck also plans to share these data with global regulatory authorities.

REFERENCES

1. KEYTRUDA® (pembrolizumab) Plus WELIREG® (belzutifan) Given as Adjuvant Therapy Reduced the Risk of Disease Recurrence or Death by 28% Compared to KEYTRUDA Monotherapy in Certain Patients With Earlier-Stage Renal Cell Carcinoma (RCC). News release. Merck. February 28, 2026. Accessed March 2, 2026. https://www.merck.com/news/keytruda-pembrolizumab-plus-welireg-belzutifan-given-as-adjuvant-therapy-reduced-the-risk-of-disease-recurrence-or-death-by-28-compared-to-keytruda-monotherapy-in-certain-patients-with/

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. ). Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA418. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16925?presentation=256660