New Protocol: Adjuvant Belzutifan with Pembrolizumab for Renal Cell Carcinoma

In the LITESPARK-022 trial, adjuvant pembrolizumab plus belzutifan significantly improved disease-free survival compared to pembrolizumab plus placebo in patients with resected clear-cell renal-cell carcinoma at increased risk for recurrence. The 24-month disease-free survival rate was 80.7% for the combination therapy versus 73.7% for pembrolizumab monotherapy, with a hazard ratio of 0.72. However, the combination therapy was associated with a higher incidence of grade 3 or higher adverse events (52.1% vs 30.2%). Overall survival data were immature, with no significant difference observed between the groups at this interim analysis.

Study

Randomized, double-blind, phase 3 trial [LITESPARK-022, NCT05239728]

Resected clear-cell RCC at increased risk for recurrence

Pembrolizumab+Belzutifan (n=921) vs Pembrolizumab+Placebo (n=920)

Efficacy

24-mo DFS: 80.7% vs 73.7% (belzutifan + pembro vs. placebo + pembro) (HR 0.72 [0.59-0.87])

24-mo OS: 96.2% vs 95.7% (HR 0.78 [0.51-1.19])

Safety

Grade >=3 AE: anemia (12.1% vs 0.4%), ALT level increased (6.4% vs 2.0%), AST level increased (3.4% vs 1.4%), diarrhea (2.4% vs 2.0%), fatigue (2.1% vs 0.7%), hypoxia (4.6% vs Not reported)

Serious adverse events: 29.5% vs 19.9%

Discontinuation of any trial regimen due to AE: 34.3% vs 19.5%