LITESPARK-012 trial misses dual primary end points in advanced ccRCC

Two investigational intensification strategies built on the esstablished first-line regimen of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) did not improve progression-free survival (PFS) or overall survival (OS) in patients with advanced clear cell renal cell carcinoma (ccRCC), according to topline results from the phase 3 LITESPARK-012 trial (NCT04736706) announced by Merck and Eisai.¹

The trial assessed the triplet regimen of pembrolizumab, lenvatinib, and belzutifan (Welireg) as well as the combination of MK-1308A, the coformulation of pembrolizumab and quavonlimab, Merck’s investigational anti-CTLA-4 antibody, plus lenvatinib compared with pembrolizumab plus lenvatinib in advanced ccRCC. At a prespecified interim analysis of the data, both combinations failed to improve the trial’s dual primary end points of PFS and OS vs first-line pembrolizumab plus lenvatinib.

The sponsors also stated that “the safety profiles of the combination regimens were consistent with those observed in previously reported studies evaluating the individual medicines and the [pembrolizumab] plus [lenvatinib] combination.”

“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,” said Corina Dutcus, MD, senior vice president and oncology global clinical development lead at Eisai Inc, in the news 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.”

About LITESPARK-012

LITESPARK-012 is a randomized, open-label phase 3 study comparing first-line combination strategies for advanced ccRCC. The trial enrolled 1688 adult patients who were randomly assigned to receive 1 of 3 regimens: pembrolizumab (400 mg IV every 6 weeks) plus lenvatinib (20 mg orally once daily) plus belzutifan (120 mg orally once daily); MK-1308A (pembrolizumab, 400 mg; quaonlimab, 25 mg) plus lenvatinib (20 mg orally once daily); or the control arm of pembrolizumab (400 mg IV every 6 weeks) plus lenvatinib (20 mg orally once daily).

The dual primary end points were PFS by blinded independent central review (BICR) and OS. Secondary end points included objective response rate, duration of response per BICR according to RECIST v1.1, and safety.

The negative results from LITESPARK-012 do not affect ongoing trials within the LITESPARK platform. Merck noted that the FDA has accepted supplemental applications based on the phase 3 LITESPARK-011 trial evaluating belzutifan plus lenvatinib in certain previously treated patients with advanced RCC, with a target action date of October 4, 2026.

“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,” concluded M. Catherine Pietanza, MD, vice president of global clinical development for Merck Research Laboratories, in the news release.¹ “While these regimens did not demonstrate the results we hoped, the data deepen our understanding of advanced renal cell carcinoma and will help shape the next generation of treatment approaches.”

REFERENCE

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 and Eisai. April 21, 2026. Accessed April 21, 2026. https://www.merck.com/news/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/