A coprimary end point in the phase 3 LEAP-010 study will not be met.
The combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) demonstrated statistically significant improvement in co-primary end points progression-free survival (PFS) and objective response rate (ORR) in comparison with pembrolizumab plus placebo in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1.1
Results from 2 interim analyses of the phase 3 LEAP-010 trial (NCT04199104) reviewed by an independent Data Monitoring Committee (DMC) were released in a Merck press release. In the second interim analysis, the combination of pembrolizumab and lenvatinib failed to demonstrate statistically significant improvement in the third primary end point of overall survival (OS) compared with pembrolizumab and placebo.
The safety profile observed in the study was consistent with prior knowledge of pembrolizumab combined with lenvatinib.
The study has been closed by collaborators Merck and Eisai because of the OS result. However, there will be a full assessment of the study data, which will be presented at a future medical meeting. Merck stated in the press release that the data will be useful for future research of pembrolizumab plus lenvatinib. The closure of LEAP-010 has no impact of other studies or indication for pembrolizumab plus lenvatinib.
“While we were initially encouraged to see that Keytruda plus Lenvima met 2 of its 3 primary end points at an earlier interim analysis, unfortunately the combination did not meet the threshold for the third primary end point of overall survival,” Corina Dutcus, MD, senior vice president, Global Clinical Development, Oncology at Eisai Inc, said in the press release. “Our clinical program is designed to help accelerate our efforts to tackle difficult-to-treat, advanced cancers, and while the outcome may not always be what we anticipate, we know that this is part of clinical development, and we remain committed to scientific exploration in pursuit of improving care for patients.”
LEAP-010 was a randomized, placebo-controlled, double-blind, phase 3 trial exploring the use of pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle with lenvatinib 20 mg orally once daily vs pembrolizumab 200 mg IV on day 1 of each 3-week cycle plus matching placebo. The 3 primary end points explored with OS, PFS, and ORR. The secondary end points of the study were duration of response, the number of patients with adverse events (AEs), and the number of patients who discontinued treatment due to an AE.2
The study enrolled patients with histologically or cytologically confirmed recurrent or metastatic HNSCC whose primary tumors were located on the oropharynx, oral cavity, hypopharynx, or larynx. Patients enrolled were required to have measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, adequately controlled blood pressure with or without antihypertensive medications, as wells as adequate organ function.
Merck and Eisai plan to inform clinical trial investigators about the study closure.1
1. Merck and Eisai provide update on phase 3 LEAP-010 trial evaluating Keytruda® (pembrolizumab) plus Lenvima® (lenvatinib) in patients with certain types of recurrent or metastatic head and neck squamous cell carcinoma. News release. August 25, 2023. Accessed August 25, 2023. https://tinyurl.com/ye8e4wza
2. A study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as first line (1L) intervention in a programmed cell death-ligand 1 (PD-L1) selected population with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) (LEAP-010) (MK-7902-010) (LEAP-10). Update August 3, 2023. Accessed August 25, 2023. https://clinicaltrials.gov/study/NCT04199104?term=NCT04199104&rank=1