Merck and Eisai’s Keytruda-Lenvima tag team can’t seem to catch a break. Following a series of trial shortfalls this year in melanoma, colorectal cancer and head and neck squamous cell carcinoma, the drug duo has missed the mark in yet another set of clinical trials—this time in non-small cell lung cancer (NSCLC).
Keytruda plus Lenvima failed to meet dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in two separate lung cancer studies, LEAP-006 and LEAP-008, Merck and Eisai said Friday.
LEAP-006 tested the combo's potential as a first-line treatment for certain adults with metastatic, nonsquamous NSCLC, while the LEAP-008 trial weighed the regimen as a second-line therapy for patients with metastatic NSCLC whose disease got worse on a combination of platinum-containing chemotherapy and a PD-1/L1 immunotherapy.
In the first-line study, investigators saw no improvement in overall survival for patients on Keytruda, Lenvima and chemotherapy versus the control regimen of Keytruda and chemotherapy, the partners said. What’s more, prior interim analyses failed to show statistically significant improvements in progression-free survival or objective response rate (ORR), which caused the study to miss a key secondary endpoint, Merck and Eisai said.
The situation was much the same in the combo regimen’s second-line trial, in which Keytruda plus Lenvima missed again on overall survival, progression-free survival and overall response rate.
Merck and Eisai did not say whether they will continue development of their combo in NSCLC. A full evaluation of the data from the studies is “ongoing," the partners said in a release.
“While these results are not what we hoped for, we are proud of the foundational role that Keytruda has established in the treatment of certain types of lung cancer, and we are committed to continuing to research how we can further improve responses to our medicines for patients with difficult-to-treat forms of the disease,” Gregory Lubiniecki, VP of global clinical development at Merck Research Laboratories, said in a release.
The Keytruda-Lenvima duo so far boasts two approvals in the U.S. The pair first clinched an accelerated nod in endometrial cancer in 2019, which was converted into a full green light in the summer of 2021. A few weeks after that, the combo scored its second thumbs up from the FDA in newly diagnosed patients with advanced kidney cancer.
Despite those prior wins, the combo has struggled significantly over the past two years.
In April, Merck and Eisai put the kibosh on LEAP-003, a phase 3 trial of Keytruda plus Lenvima as an initial treatment in unresectable or metastatic melanoma, after an independent data monitoring committee recommended the study be stopped. In an interim analysis, the combination failed to help stave off death better than Keytruda alone.
Keytruda and Lenvima also missed the mark on overall survival in another phase 3 trial, LEAP-017, which pitted the combination against unresectable and metastatic colorectal cancer.
And in August, the two companies decided to shut down a phase 3 trial testing their PD-1/TKI combo in newly diagnosed recurrent or metastatic, PD-L1 positive head and neck squamous cell carcinoma.
Although Lenvima helped Keytruda trigger more tumor responses and delayed the progression of cancer, the combo failed to significantly extend patients’ lives in the LEAP-010 trial.
Prior to 2023, meanwhile, Merck and Eisai’s combo regimen failed to extend patients’ lives over Keytruda monotherapy in newly diagnosed NSCLC with PD-L1 expression covering at least 1% of tumor cells. The combo also missed the mark in bladder cancer and liver cancer.
Merck and Eisai are continuing to test their Keytruda-Lenvima combo across a range of potential oncology indications, including endometrial carcinoma, hepatocellular carcinoma, head and neck cancer and gastric cancer.