At a Glance
- 30% risk reduction: Directly matches the reported 30% reduction in progression or death risk versus cabozantinib.
- PFS medians: 14.8 months (WELIREG + LENVIMA) vs. 10.7 months (cabozantinib).
- Higher ORR/DOR: Confirmed at 52.6% ORR and 23.0 months median DOR for the combo versus lower rates for cabozantinib.
- Safety profile: Consistent with known profiles; Grade ≥3 TRAEs in 71.6% (combo) vs. 65.8% (cabozantinib), with comparable discontinuations.
- sNDAs/PDUFA: FDA accepted both applications post-data, targeting October 4, 2026
Written By: Chikkula Pavan Kumar PharmD
Reviewed By: Pharmacally Editorial Team
Merck and Eisai announced the first results from the Phase 3 LITESPARK-011 trial, showing their dual oral regimen of WELIREG (belzutifan) plus LENVIMA (lenvatinib) significantly improved progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC) after PD-1/PD-L1 therapy. The data, presented as a late-breaking abstract at the 2026 ASCO Genitourinary Cancers Symposium, support two FDA-accepted supplemental New Drug Applications with a PDUFA date of October 4, 2026.
At a median follow-up of 29.0 months, WELIREG plus LENVIMA reduced the risk of disease progression or death by 30% versus cabozantinib. Median PFS reached 14.8 months for the combination arm compared to 10.7 months for cabozantinib.
A trend toward better overall survival emerged, with median OS of 34.9 months versus 27.6 months; the trial continues.
Secondary Endpoints
Confirmed objective response rate (ORR) favoured the combination at 52.6% versus 39.6% for cabozantinib at the first interim analysis. Median duration of response (DOR) was 23.0 months for WELIREG plus LENVIMA compared to 12.3 months at the second analysis
Safety Profile
Grade ≥3 treatment-related adverse events (TRAEs) occurred in 71.6% of patients on WELIREG plus LENVIMA versus 65.8% on cabozantinib; discontinuations were similar at 11.1% and 11.3%.
Serious AEs affected 51.6% versus 43.9%, with treatment-related deaths in 5.4% (thrombotic microangiopathy, pneumonitis) versus 3.2% (hemoptysis).
For full details on adverse events, warnings, and precautions including anemia, hypoxia for WELIREG and hypertension, hepatotoxicity, cardiac dysfunction for LENVIMA refer to the WELIREG Prescribing Information and LENVIMA Prescribing Information.
Dr. Robert Motzer, principal investigator from Memorial Sloan Kettering, highlighted the 30% risk reduction and 52.6% ORR as a “critical step forward” in a challenging post-immunotherapy setting.
Dr. M. Catherine Pietanza, Vice President, Global Clinical Development said The LITESPARK-011 trial showcases the novel WELIREG plus LENVIMA combo’s potential for meaningful benefits in advanced RCC post-PD-1/L1 therapy, marking key progress and Merck’s dedication to innovative patient care.
Eisai’s Dr. Corina Dutcus said LITESPARK-011 bolsters LENVIMA’s RCC role and this combo’s promise for unmet needs; regulatory filing acceptance is a milestone, with gratitude to patients and investigators for advancing approval.
LITESPARK-011 (NCT04586231) enrolled 747 patients with advanced clear cell RCC post-PD-1/L1 therapy, randomizing them to WELIREG (120 mg daily) plus LENVIMA (20 mg daily) or cabozantinib (60 mg daily). WELIREG is already approved for advanced RCC post-PD-1/PD-L1 and 1-2 VEGF-TKIs based on LITESPARK-005.
Reference
WELIREG® (belzutifan) Plus LENVIMA® (lenvatinib) Reduced the Risk of Disease Progression or Death by 30% Compared to Cabozantinib in Certain Previously Treated Patients With Advanced Renal Cell Carcinoma (RCC), 28 February 2026, WELIREG® (belzutifan) Plus LENVIMA® (lenvatinib) Reduced the Risk of Disease Progression or Death by 30% Compared to Cabozantinib in Certain Previously Treated Patients With Advanced Renal Cell Carcinoma (RCC) – Merck.com
A Study of Belzutifan (MK-6482) in Combination with Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011), ClinicalTrials.gov ID NCT04586231, https://clinicaltrials.gov/study/NCT04586231
About Writer
Chikkula Pavan Kumar, PharmD
He is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication