On February 28, 2026 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the presentation of results from the pivotal Phase 3 LITESPARK-022 trial evaluating KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with WELIREG (belzutifan), Merck’s first-in-class, oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, given in the adjuvant setting, for patients with clear cell renal cell carcinoma (RCC) following nephrectomy. These late-breaking data will be presented for the first time today during an oral abstract session at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium (abstract #LBA418) and are included in the official ASCO (Free ASCO Whitepaper) GU Press Program.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At the first pre-specified interim analysis (median follow-up of 28.4 months [range, 15.0-40.1 months]), KEYTRUDA plus WELIREG given in the adjuvant setting significantly improved disease-free survival (DFS), the study’s primary endpoint, reducing the risk of disease recurrence or death by 28% (HR=0.72 [95% CI 0.59-0.87]; p=0.0003) compared to KEYTRUDA plus placebo. Median DFS was not reached in either arm; the estimated 24-month DFS rate was 80.7% (95% CI, 77.7-83.2) for the KEYTRUDA plus WELIREG arm and was 73.7% (95% CI, 70.6-76.6) for the KEYTRUDA plus placebo arm. As previously reported, the trial will continue to evaluate overall survival (OS), a key secondary endpoint.

"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 Dr. Toni K. Choueiri, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg professor of medicine, Harvard Medical School. "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."

"LITESPARK-022 is a critical part of our comprehensive RCC clinical development program, and the Phase 3 results presented at ASCO (Free ASCO Whitepaper) GU underscore the importance of KEYTRUDA and WELIREG in helping to treat patients with certain types of renal cell carcinoma," said Dr. M. Catherine Pietanza, vice president, Global Clinical Development, Merck Research Laboratories. "These findings represent the first positive Phase 3 data for WELIREG in earlier stages of disease, as well as the first positive Phase 3 results for a HIF‑2α inhibitor and immunotherapy combination, reinforcing our commitment to exploring novel treatment approaches to improve upon established treatment paradigms for patients in need."

The safety profile of KEYTRUDA plus WELIREG was consistent with that observed in previously reported studies for both agents; no new safety signals were observed. Of patients enrolled, 69.5% of those in the KEYTRUDA plus WELIREG arm and 71.1% of those in the KEYTRUDA plus placebo arm completed the assigned treatment. Among treated patients, Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 52.1% of patients who received KEYTRUDA plus WELIREG and 30.2% of patients who received KEYTRUDA plus placebo. The most common Grade ≥3 TEAEs were anemia (12.1% versus 0.5%), increased alanine aminotransferase (ALT) (6.4% versus 2.0%) and hypoxia (4.6% versus 0%). Grade 5 treatment-emergent (1.1% versus 1.2%) and treatment-related adverse events (0.3% versus 0.3%) were similar between treatment arms.

Based on data from the LITESPARK-022 trial, the U.S. Food and Drug Administration (FDA) has accepted for priority review supplemental applications seeking approval of WELIREG in combination with KEYTRUDA or KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) for the adjuvant treatment of adult patients with RCC with a clear cell component with increased risk of recurrence following nephrectomy. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action date, of June 19, 2026 for the WELIREG sNDA and the KEYTRUDA and KEYTRUDA QLEX sBLAs. Merck will also discuss these data with global regulatory authorities.

KEYTRUDA is approved for the adjuvant treatment of certain patients with RCC in the U.S., Canada, European Union (EU), Japan and other countries worldwide based on data from KEYNOTE-564.

WELIREG is approved in over 45 countries including the U.S., Canada, EU, and Japan for the treatment of adult patients with advanced RCC following a PD-1/PD-L1 inhibitor and 1-2 VEGF-TKIs based on results from the Phase 3 LITESPARK-005 trial.

Merck has an industry-leading clinical development program in RCC, leveraging multiple approved therapeutic options across multiple settings, including adjuvant and advanced disease.

About LITESPARK-022

LITESPARK-022 is a multicenter, randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT05239728) evaluating WELIREG in combination with KEYTRUDA compared to KEYTRUDA plus placebo for the treatment of patients with clear cell RCC following nephrectomy. The primary endpoint is DFS, and key secondary endpoints include OS, safety and quality of life outcomes. The trial enrolled 1,841 patients who were randomized to receive either:

WELIREG (120 mg orally once daily for approximately one year) plus KEYTRUDA (400 mg intravenously every six weeks for approximately one year), or;
KEYTRUDA plus placebo.
About renal cell carcinoma

Renal cell carcinoma is the most common type of kidney cancer, with about nine out of 10 kidney cancer diagnoses being RCC. In 2022, there were about 435,000 new cases of kidney cancer diagnosed and approximately 156,000 deaths from the disease worldwide. Renal cell carcinoma is about twice as common in men as in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Approximately 30% of patients with kidney cancer are diagnosed at an advanced stage.

(Press release, Merck & Co, FEB 28, 2026, View Source [SID1234663144])