Merck and Eisai’s collaborative effort with Keytruda and Lenvima faces yet another setback in their quest to combat cancer. Despite previous disappointments this year in melanoma, colorectal cancer, and head and neck squamous cell carcinoma trials, the duo has encountered yet another challenge, this time in non-small cell lung cancer (NSCLC).
Keytruda, when combined with Lenvima, fell short of achieving the dual primary endpoints concerning overall survival (OS) and progression-free survival (PFS) in two separate clinical trials: LEAP-006 and LEAP-008, as reported by Merck and Eisai on Friday.
LEAP-006 explored the combination’s potential as a first-line treatment for specific adults afflicted with metastatic, nonsquamous NSCLC. Meanwhile, LEAP-008 assessed the regimen’s suitability as a second-line therapy for patients with metastatic NSCLC, whose condition had worsened following treatment with platinum-containing chemotherapy and a PD-1/L1 immunotherapy.
In the first-line study, the addition of Keytruda, Lenvima, and chemotherapy did not yield an improvement in overall survival when compared to the control regimen involving Keytruda and chemotherapy alone. Furthermore, prior interim analyses failed to demonstrate statistically significant enhancements in progression-free survival or objective response rate (ORR), leading to the study’s failure to meet a crucial secondary endpoint, as disclosed by Merck and Eisai.
A similar scenario unfolded in the second-line trial, where Keytruda plus Lenvima once again missed the mark in terms of overall survival, progression-free survival, and overall response rate. The partners did not divulge whether they intend to continue the development of this combination therapy for NSCLC. They stated that a comprehensive assessment of the trial data is currently underway.
“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
Keytruda and Lenvima have previously garnered two approvals in the United States, initially securing accelerated approval in endometrial cancer in 2019, which was later converted into full-fledged approval in the summer of 2021. Shortly after, the duo received a second green light from the FDA for newly diagnosed patients with advanced kidney cancer.
Despite these early successes, the combination has faced substantial challenges over the past two years. In April, Merck and Eisai terminated LEAP-003, a phase 3 trial of Keytruda plus Lenvima as the initial treatment for unresectable or metastatic melanoma, following a recommendation from an independent data monitoring committee to halt the study. An interim analysis indicated that the combination did not improve patient survival compared to Keytruda alone.
Additionally, Keytruda and Lenvima failed to meet overall survival expectations in another phase 3 trial, LEAP-017, which involved unresectable and metastatic colorectal cancer.
In August, both companies decided to discontinue a phase 3 trial assessing their PD-1/TKI combination in newly diagnosed recurrent or metastatic, PD-L1 positive head and neck squamous cell carcinoma.
Although Lenvima demonstrated efficacy in triggering more tumor responses and delaying cancer progression, it fell short of significantly extending patient lifespans in the LEAP-010 trial. Prior to 2023, the Keytruda-Lenvima combination failed to outperform Keytruda monotherapy in extending patient lives in newly diagnosed NSCLC cases with PD-L1 expression covering at least 1% of tumor cells. Furthermore, the combination proved ineffective in trials related to bladder cancer and liver cancer.
Merck and Eisai continue to explore the potential of their Keytruda-Lenvima combination in various oncology indications, including endometrial carcinoma, hepatocellular carcinoma, head and neck cancer, and gastric cancer.