ASCO GU 2026: Adjuvant Pembrolizumab + Belzutifan versus Pembrolizumab for Clear Cell RCC: The Randomized Phase 3 LITESPARK-022 Study

(UroToday.com) The 2026 GU ASCO annual meeting featured a kidney cancer session and a presentation by Dr. Toni K. Choueiri discussing results from the randomized phase 3 LITESPARK-022 study assessing adjuvant pembrolizumab + belzutifan versus pembrolizumab for clear cell RCC. Adjuvant pembrolizumab is a standard of care for patients with clear cell RCC at increased risk of recurrence following nephrectomy based on the phase 3 KEYNOTE-564 study.^1,2 Belzutifan is a potent, selective HIF-2alpha inhibitor with established efficacy in patients with advanced RCC treated with prior immunotherapy and VEGFR-TKI therapy.³ Thus, combination strategies may further improve outcomes in this setting. At ASCO GU 2026, Dr. Choueiri and colleagues presented results from the phase 3, double-blind LITESPARK-022 study of pembrolizumab + belzutifan versus pembrolizumab + placebo in patients with clear cell RCC at increased risk of recurrence post nephrectomy.

Patients had clear cell RCC stage M0 and intermediate-high (pT2 Gr 4 or sarcomatoid, or pT3 any Gr, N0) or high (pT4 any Gr, N0, or any pT and Gr, N+) risk of recurrence after nephrectomy, or clear cell RCC stage M1 with no evidence of disease (M1 NED) after surgery. Patients were randomized 1:1 to receive 9 doses of IV pembrolizumab 400 mg Q6W (~1 year) with either oral belzutifan 120 mg QD or placebo.

The primary endpoint was disease free survival by investigator, and secondary endpoints included overall survival (key secondary endpoint) and safety. Results were presented from the first interim analysis (after 87% of disease free survival events occurred with a minimum of 15 months of follow-up).

Overall, 1,841 patients were randomized (921 to pembrolizumab + belzutifan and 920 to pembrolizumab + placebo), and as of August 23, 2025, the median follow-up was 28.4 months (range: 15.0–40.1). The patient disposition is highlighted in the following figure:

The baseline characteristics were well balanced between the two groups. Approximately 85% of patients were intermediate/high risk and ~10% had sarcomatoid features:

Pembrolizumab + belzutifan significantly improved disease free survival versus pembrolizumab + placebo (HR 0.72, 95% CI 0.59–0.87; p = 0.0003), with the median disease free survival not reached in both arms. The estimated 24-month disease free survival rate was 80.7% (95% CI, 77.7–83.2) versus 73.7% (95% CI, 70.6–76.6), respectively:

The disease free survival benefit of pembrolizumab + belzutifan generally favored all of the subgroups:

Overall survival was immature at the first interim analysis with a total of 87 overall survival events (38 in the pembrolizumab + belzutifan arm versus 49 in the pembrolizumab + placebo arm) and did not reach statistical significance (HR 0.78, 95% CI 0.51–1.19; p = 0.1220) at 29% of the events needed for final overall survival analysis:

Overall, 70% of the pembrolizumab + belzutifan arm and 71% of the pembrolizumab + placebo arm completed the assigned treatment. Among treated patients, grade ≥3 treatment emergent adverse events occurred in 52.1% of patients who received pembrolizumab + belzutifan and 30.2% who received pembrolizumab + placebo

The most common grade ≥3 treatment emergent adverse events were anemia (12.1% versus 0.4%), increased ALT (6.4% versus 2.0%), and hypoxia (4.6% versus 0%):

The following table summarizes the management of anemia in each of the treatment groups:

Grade 5 treatment-emergent (1.1% versus 1.2%, respectively) and treatment-related (0.3% versus 0.3%) adverse events were similar between arms.

Dr. Choueiri concluded his presentation discussing results from the randomized phase 3 LITESPARK-022 study assessing adjuvant pembrolizumab + belzutifan versus pembrolizumab for clear cell RCC with the following take-home points:

Pembrolizumab + belzutifan showed a statistically significant and clinically meaningful disease free survival improvement versus pembrolizumab monotherapy in participants with clear cell RCC at increased risk of recurrence post nephrectomy
- The disease free survival benefit was generally consistent across prespecified subgroups
Additional follow-up is planned for the key secondary endpoint of overall survival
The safety profile of pembrolizumab + belzutifan was manageable, with a low rate of adverse events leading to the discontinuation of both study drugs
- Overall safety was consistent with the expected profiles of each individual drug
LITESPARK-022 is the first adjuvant phase 3 trial in RCC to show a significant benefit for a combination treatment versus an active immunotherapy comparator
These results support the addition of belzutifan to standard of care adjuvant pembrolizumab for patients with clear cell RCC at increased risk of recurrence

Presented by: Toni K. Choueiri, MD, Dana Farber Cancer Institute, Boston, MA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 26 – Sat, Feb 28, 2026.

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