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LITESPARK-022

Adjuvant pembrolizumab plus belzutifan versus pembrolizumab plus placebo in clear-cell renal-cell carcinoma at increased risk of recurrence (MK-6482-022, LITESPARK-022)

Phase 3NCT05239728

Population
Clear-cell renal-cell carcinoma at increased risk of recurrence after nephrectomy.
Design
Double-blind phase 3 trial, randomised 1:1. Pembrolizumab 400 mg intravenously every 6 weeks (up to 9 doses) plus daily oral belzutifan 120 mg or placebo for up to 1 year. Primary endpoint investigator-assessed disease-free survival; secondary endpoints included overall survival and safety. Both arms received pembrolizumab. The ClinicalTrials.gov record lists estimated enrolment of 1800.
Primary endpoint
DFS
Arms
  • Pembrolizumab plus belzutifan (experimental, n = 921): Pembrolizumab 400 mg every 6 weeks (up to 9 doses) plus belzutifan 120 mg orally daily, up to 1 year
  • Pembrolizumab plus placebo (control, n = 920): Pembrolizumab 400 mg every 6 weeks (up to 9 doses) plus placebo orally daily, up to 1 year
People
Choueiri TK
DFSHR 0.72 (95% CI 0.59–0.87)Δ 24-month DFS+7 pointsOSHR 0.78 (95% CI 0.51–1.19)Δ 24-month OS+0.5 points
Show the numbers
Results reported for LITESPARK-022
EndpointAnalysisPembrolizumab plus belzutifanPembrolizumab plus placeboEffect
DFSRandomised patients (analysis population not stated in the abstract)Disease-free survival as assessed by the investigator.interimmedian follow-up 28.4 monthsChoueiri 202680.7% at 2 y73.7% at 2 yHR 0.72 (95% CI 0.59–0.87)P<0.001Median time from randomisation to data cutoff 28.4 months (range 15.0 to 40.1). The control arm received pembrolizumab, so this compares belzutifan plus pembrolizumab with pembrolizumab alone, not with placebo. Grade 3 or higher adverse events occurred in 52.1% with pembrolizumab-belzutifan and 30.2% with pembrolizumab-placebo. The FDA letter describes the supporting analysis as Interim Analysis 1.
OSRandomised patients (analysis population not stated in the abstract)interimmedian follow-up 28.4 monthsChoueiri 202696.2% at 2 y95.7% at 2 yHR 0.78 (95% CI 0.51–1.19)P=0.24Overall survival did not differ significantly at this interim analysis, with 29% of the final-analysis events observed; two-sided P.
Results reported for LITESPARK-022
EndpointAnalysisPembrolizumab plus belzutifanPembrolizumab plus placeboEffect
DFSRandomised patients (analysis population not stated in the abstract)Disease-free survival as assessed by the investigator.interimmedian follow-up 28.4 monthsChoueiri 202680.7% at 2 y73.7% at 2 yHR 0.72 (95% CI 0.59–0.87)P<0.001Median time from randomisation to data cutoff 28.4 months (range 15.0 to 40.1). The control arm received pembrolizumab, so this compares belzutifan plus pembrolizumab with pembrolizumab alone, not with placebo. Grade 3 or higher adverse events occurred in 52.1% with pembrolizumab-belzutifan and 30.2% with pembrolizumab-placebo. The FDA letter describes the supporting analysis as Interim Analysis 1.
OSRandomised patients (analysis population not stated in the abstract)interimmedian follow-up 28.4 monthsChoueiri 202696.2% at 2 y95.7% at 2 yHR 0.78 (95% CI 0.51–1.19)P=0.24Overall survival did not differ significantly at this interim analysis, with 29% of the final-analysis events observed; two-sided P.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
DFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
DFS0.720.59–0.87
OS0.780.51–1.19
Primary publication: Choueiri TK, Motzer RJ, Karam JA, Yip W, Suárez C, Ye D, et al. Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma. N Engl J Med. 2026;395(1):32-43. PubMedDOI

Appears in

Sources

  1. Choueiri TK, Motzer RJ, Karam JA, Yip W, Suárez C, Ye D, et al. Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma. N Engl J Med. 2026;395(1):32-43.

    PubMedDOI