A triplet regimen comprising Merck’s Welireg and PD-1 blockbuster Keytruda and Eisai’s Lenvima flopped in a Phase 3 renal cell carcinoma trial.
Merck and Eisai are looking at an investigational regimen of three FDA-approved therapies for the treatment of renal cell carcinoma. Tuesday, however, a late-stage readout found that the three-drug combo showed no significant survival benefit.
In the Phase 3 LITESPARK-012 study, the partners combined Merck’s mega-blockbuster PD-1 inhibitor Keytruda with the pharma’s oral HIF-2α inhibitor Welireg and Eisai’s tyrosine kinase inhibitor Lenvima. All three drugs have previously been cleared by the FDA for various cancers.
Merck and Eisai did not provide specific data from LITESPARK-012 in their news release on Tuesday, disclosing only that the triplet therapy “did not meet the dual primary endpoints” of overall survival and progression-free survival. The companies were testing the combo regimen as a first-line therapy for renal cell carcinoma (RCC). Controls were given Keytruda plus Lenvima.
These data represent a “triplet trip-up” for Merck and Eisai, according to analysts at William Blair, who wrote in a Monday note that the miss “could theoretically open a path” for competitors. In particular, William Blair pointed to Exelixis and its oral kinase blocker zanzalintinib.
Merck is currently testing zanzalintinib with Welireg in the Phase 3 LITESPARK-033 trial in RCC. The study is set to complete in 2032. Exelixis is up just over 2% to $44.56 in premarket trading on Tuesday.
LITESPARK-012’s failure on Tuesday does not affect the other ongoing trials under the LITESPARK program, according to Merck and Eisai’s news release.
The companies are “disappointed” with the survival miss, but such study failures “play an important role in shaping health care providers’ perspectives as the treatment paradigm” for RCC evolves, Corina Ductus, Oncology Global Clinical Development Lead at Eisai, said in a prepared statement.
Merck and Eisai have a long history of working together to advance cancer treatment. Their partnership stretches as far back as 2015, when the companies inked a clinical trial collaboration to test Keytruda with Lenvima and Eisai’s breast cancer drug Halaven. In 2018, the partners reaffirmed their commitment to each other when Merck bet up to $5.76 billion to develop and commercialize a combo regimen of Keytruda and Lenvima.
Over the years, the collaboration has had its fair share of successes and stumbles. In August 2021, for instance, the FDA cleared the Keytruda-Lenvima combo as a first-line therapy for advanced RCC. In October last year, however, the doublet, when used alongside transarterial chemoembolization, failed to significantly boost overall survival in a Phase 3 hepatocellular carcinoma study.
