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This is the first positive Phase 3 trial for WELIREG in earlier-stage disease, the first positive results for a HIF-2α inhibitor and immunotherapy combination and the first study in earlier-stage disease, regardless of tumor type, to demonstrate a disease-free survival improvement compared to KEYTRUDA
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Based on these data, the U.S. FDA has accepted for priority review supplemental applications for WELIREG in combination with KEYTRUDA or KEYTRUDA QLEX™ for the adjuvant treatment of certain patients with RCC
February 28, 2026--RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced 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) Genitourinary (GU) Cancers Symposium (abstract #LBA418) and are included in the official ASCO GU Press Program.
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 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.
About Merck’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer.
About Merck’s research in genitourinary cancers
Merck is advancing research aimed at helping transform the treatment landscape and broaden options for people with genitourinary (GU) cancers, including bladder, kidney and prostate cancers. Globally, GU cancers account for an estimated 2.6 million new cancer diagnoses each year, equaling over 1 in 8 of all cancer incidences. Through a robust clinical development program with more than 50 ongoing clinical trials evaluating more than 22,000 patients around the world, Merck is investigating the potential of several portfolio medicines and pipeline assets, leveraging multiple novel combination strategies, across various stages of disease, to help address unmet needs in GU cancers.
About WELIREG® (belzutifan) 40 mg tablets, for oral use
WELIREG, Merck’s first-in-class hypoxia-inducible factor 2 alpha (HIF-2α) inhibitor, is an orally administered small-molecule designed to reduce transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis and tumor growth. By inhibiting HIF-2α signaling, WELIREG aims to disrupt key pathways certain tumors may use to adapt to low-oxygen conditions, including those that help promote abnormal blood vessel formation and support tumor survival.
WELIREG has received regulatory approvals in patients with certain von Hippel-Lindau (VHL) disease-associated tumors, renal cell carcinoma (RCC) and in pheochromocytoma or paraganglioma (PPGL). As part of a broader clinical program, Merck continues to research WELIREG monotherapy and combination approaches for people with RCC and selected solid tumors across a range of treatment settings, to further define where HIF-2a inhibition may provide clinical benefit.
About KEYTRUDA® (pembrolizumab) injection for intravenous use, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
About KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) injection for subcutaneous use
KEYTRUDA QLEX is a fixed-combination drug product of pembrolizumab and berahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody and berahyaluronidase alfa enhances dispersion and permeability to enable subcutaneous administration of pembrolizumab. KEYTRUDA QLEX is administered as a subcutaneous injection into the thigh or abdomen, avoiding the 5 cm area around the navel, over one minute every three weeks (2.4 mL) or over two minutes every six weeks (4.8 mL).
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.