Merck and Eisai’s Phase 3 LITESPARK-012 study failed Tuesday. The trial combined Keytruda, Welireg, and Eisai’s tyrosine kinase inhibitor Lenvima as a first-line therapy for renal cell carcinoma. It missed both primary endpoints: overall survival and progression-free survival.
All three drugs are already FDA-cleared for various cancers. Controls received the already-cleared Keytruda-Lenvima doublet. Merck and Eisai didn’t disclose specific data, saying only that the triplet “did not meet the dual primary endpoints.”
Merck bet up to $5.76 billion in 2018 to develop and commercialize Keytruda-Lenvima. The two companies have collaborated since 2015, when they first inked a clinical trial deal to test Keytruda with Lenvima and Eisai’s breast cancer drug Halaven.
That doublet got cleared for advanced RCC in August 2021, then failed a Phase 3 hepatocellular carcinoma study in October 2025. Adding Welireg, Merck’s oral HIF-2α inhibitor, was supposed to push the triplet past the doublet. It didn’t.
William Blair analysts called the result a “triplet trip-up” and wrote that the miss “could theoretically open a path” for competitors, specifically Exelixis and its oral kinase blocker zanzalintinib. Exelixis shares were up just over 2% to $44.56 in premarket trading Tuesday. Merck itself is already testing zanzalintinib with Welireg in the Phase 3 LITESPARK-033 trial.
LITESPARK-033 won’t complete until 2032. The LITESPARK-012 failure doesn’t affect the other ongoing LITESPARK trials.
Sarah Chen