LITESPARK-012 Trial Does Not Meet Primary End Point for Advanced RCC Group

An investigational combination evaluating pembrolizumab (Keytruda), lenvatinib (Lenvima), and belzutifan (Welireg) did not meet the coprimary end points of progression-free survival (PFS) and overall survival (OS) vs as a frontline treatment option for patients with renal cell carcinoma (RCC) in the phase 3 LITESPARK-012 trial (NCT04736706), according to a news release from the developers, Merck and Eisai.¹

The study assessed pembrolizumab, lenvatinib, and belzutifan; MK-1308A, the co-formulation of pembrolizumab plus quavonlimab and lenvatinib; compared with pembrolizumab plus lenvatinib.

Additionally, the safety profiles of the belzutifan-based combination regimens were consistent with pembrolizumab/lenvatinib in prior reports. Moreover, a full evaluation of the data is ongoing, with the developers working with investigators to exhibit the full results. Moreover, the developers have asserted that the LITESPARK-012 results will not impact other ongoing trials within the LITESPARK program.

"With the LITESPARK-012 trial, we explored whether combining therapies with established activity could improve upon well-established standards set by [pembrolizumab]-based regimens, reflecting our commitment to continuously explore ways to improve outcomes for the kidney cancer community," M. Catherine Pietanza, MD, vice president of Global Clinical Development at Merck Research Laboratories, wrote in the news release.¹ "While these regimens did not demonstrate the results we hoped, the data deepen our understanding of advanced [RCC] and will help shape the next generation of treatment approaches."

LITESPARK-012 Trial Design

The LITESPARK-012 trial enrolled 1688 patients with histologically confirmed clear cell RCC who did not receive prior systemic therapy for advanced disease and randomly assigned them to either treatment arm.² In each arm, pembrolizumab or its coformulation was given intravenously every 6 weeks at 400 mg, lenvatinib was given orally once daily at 20 mg. In the belzutifan-containing arm, belzutifan was given orally once daily at 120 mg, and in the MK-1308A arm, quavonlimab was given at 25 mg intravenously every 6 weeks.

Treatment with all agents continued in the absence of protocol-specified discontinuation criteria, with pembrolizumab/MK-1308A given for a maximum of 2 years. Belzutifan and lenvatinib were given as part of a combination or as a single agent until disease progression or other discontinuation criteria met.

The coprimary end points were PFS by blinded independent central review per RECIST v1.1 guideline and OS. Secondary end points in the trial included objective response rate, duration of response by BICR per RECIST v1.1 guidelines, and safety.

"While we are disappointed that LITESPARK-012 did not meet its primary end points, the findings reinforce the central role of [pembrolizumab] plus [lenvatinib] in the first-line treatment of patients with advanced renal cell carcinoma," Corina Dutcus, MD, senior vice presidentand Oncology Global Clinical Development Lead at Eisai, stated in the release.¹ "Findings from trials such as this play an important role in shaping health care providers’ perspectives as the treatment paradigm for advanced renal cell carcinoma continues to evolve. We are committed to advancing the care of people living with this disease and we are grateful to the patients, caregivers and investigators whose participation and dedication made this research possible."

Patients 18 years or older with confirmed RCC with a clear cell component, adequately controlled blood pressure, adequate organ function, and no bone resorptive therapy within 2 weeks of study start were eligible for study enrollment. Exclusion criteria included a having concurrent malignancy that is progressing or having required active treatment within 3 years of study start, having undergone major surgery within 4 weeks of random assignment, the presence of central nervous metastases, or having received radiotherapy within 2 weeks prior to initial study dose.

References

1. Merck and Eisai provide update on phase 3 LITESPARK-012 Trial evaluating first-line combination treatments for certain patients with advanced renal cell carcinoma (RCC). News release. Merck, Elsai. April 21, 2026. Accessed April 21, 2026. https://tinyurl.com/4kfyfwzp
2. A study of pembrolizumab (MK-3475) in combination with belzutifan (MK-6482) and lenvatinib (MK-7902), or pembrolizumab/​quavonlimab (MK-1308A) in combination with lenvatinib, versus pembrolizumab and lenvatinib, for treatment of advanced clear cell renal cell carcinoma (MK-6482-012). ClinicalTrials.gov. Updated November 18, 2024. Accessed April 21, 2026. https://tinyurl.com/4d24suab