MSD, Eisai report setback in first-line kidney cancer trial
A combination regimen for kidney cancer treatment based on MSD's Welireg has failed a phase 3 trial, denting the company's plans to move the drug into the frontline setting.
The phase 3 LITESPARK-012 trial is testing triplet therapy with oral HIF-2 alpha inhibitor Welireg (belzutifan) given alongside MSD's PD-1 inhibitor Keytruda (pembrolizumab) and Eisai's multikinase inhibitor Lenvima/Kisplyx (lenvatinib) in advanced renal cell carcinoma (RCC), the most common form of kidney cancer.
Another cohort was also comparing a coformulation of pembrolizumab with MSD's experimental CTLA4 inhibitor quavonlimab plus Lenvima to Keytruda/Lenvima alone, but neither of the triple-drug regimens was able to improve progression-free survival (PFS) and overall survival (OS) compared to the control treatment.
Keytruda plus Lenvima has been approved as a first-line therapy for advanced RCC since 2021, while Welireg was cleared in 2023 for RCC patients previously treated with PD-1/L1 and VEGF-targeted therapies.
Originally launched to treat rare disease von Hippel-Lindau (VHL) syndrome in 2021, extending Welireg's label into RCC has made the drug one of MSD's fastest-growing products, with sales rising 41% to $716 million in 2025 and previously tipped to cross the $1 billion threshold this year.
The setback in LITESPARK-012 dents the prospects for Welireg, as well as the pembrolizumab/quavonlimab combination codenamed MK-1308A. MSD – known as Merck & Co in the US and Canada – said the results "deepen our understanding" of advanced RCC, while Eisai said the study at least reinforced the central role of Keytruda/Lenvima in previously-untreated patients with this form of cancer.
MSD and Eisai have other shots on goal for Welireg, however, and have already filed for FDA approval of a Welireg/Lenvima dual regimen in advanced RCC that has progressed despite prior PD-1/PD-L1 inhibitor treatment, based on the results of the LITESPARK-011 trial, with a decision due in October.
Doublet therapy with Welireg and Keytruda extended PFS when compared to Keytruda plus placebo in the adjuvant setting in the LITESPARK-022 trial, while MSD is also comparing Welireg to Exelixis' follow-up to multikinase inhibitor Cabometyx (cabozantinib) – zanzalintinib – as a treatment delivered after adjuvant use of PD-1/PD-L1 inhibitors in the LITESPARK-033 trial.
The prospects for MK-1308A now look decidedly rocky, as the advanced RCC indication is the only one listed in MSD's R&D pipeline, and LITESPARK-012 is the only phase 3 trial recorded for the coformulation. However, some phase 2 studies remain active, according to the clinicaltrials.gov registry.
