Lenvatinib mesylate, an oral tyrosine kinase inhibitor, will continue to be developed and commercialized worldwide by its creator, Japan’s Eisai Co. Ltd, in a strategic collaboration with Merck, which is better known as MSD outside of the United States and Canada. The partnership between the 2 companies was announced on March 7.
Roger M. Perlmutter, MD, PhD
Lenvatinib mesylate (Lenvima), an oral tyrosine kinase inhibitor (TKI), will continue to be developed and commercialized worldwide by its creator, Japan’s Eisai Co. Ltd, in a strategic collaboration with Merck, which is better known as MSD outside of the United States and Canada. The partnership between the 2 companies was announced on March 7.
Eisai and Merck will work jointly on the development of lenvatinib mesylate as both monotherapy and in combination with Merck’s pembrolizumab (Keytruda), a PD-1 inhibitor. The combination regimen has already been granted a Breakthrough Therapy designation from the FDA for the treatment of patients with advanced and/or metastatic renal cell carcinoma (RCC), based on the ongoing phase Ib/II Study 111/KEYNOTE-146 trial that is investigating the combination in select solid tumors.
The phase Ib portion of the study enrolled 13 patients with metastatic solid tumors, 8 of whom had RCC that progressed after treatment with approved therapies and who had an ECOG performance status ≤1. Patients began treatment with 24 mg daily lenvatinib but the dosage was reduced to 20 mg per day based on toxicity. This dosage of lenvatinib advanced to the phase 2 portion, which included 22 RCC patients with measurable disease who had undergone up to 2 prior lines of systemic therapy.
The combination induced an objective response rate (ORR) of 83% after 24 weeks of treatment in patients who had not previously been treated, and the ORR was 50% in previously treated patients. All responses were partial responses and an additional 10 patients achieved stable disease. The median duration of response was not yet reached for the total cohort and the treatment-naïve cohort. The median duration of response was 8.5 months in the pretreated cohort.
“Aiming to maximize the potential of Lenvima and expedite the creation of innovative treatments in this age of ‘Cancer Evolution,’ we have entered into this collaboration with Merck who developed the antiPD-1 antibody Keytruda,” commented Haruo Naito, representative corporate officer and CEO of Eisai Co., Ltd, in a statement. “By providing new treatment options, including for refractory cancers with no hopes for a cure to date, we are striving to further contribute to increasing the benefits provided to patients and their families.”
The novel agent is currently FDA approved as a monotherapy for patients with thyroid cancer and in combination with everolimus (Afinitor) for the treatment of patients with RCC who have failed previous therapies. The phase III Study 307 trial sponsored by Eisai is ongoing to evaluate the efficacy and safety of lenvatinib mesylate plus pembrolizumab or lenvatinib mesylate plus everolimus versus chemotherapy alone in patients with RCC.
Additionally, applications for the regulatory approval of lenvatinib mesylate monotherapy have been submitted in the United States, Europe, Japan, China, and additional countries, as a treatment for patients with hepatocellular carcinoma (HCC).
Under the agreement, Eisai will book product sales globally for the TKI, while Eisai and Merck will share gross profits equally. All expenses, including trials and studies for lenvatinib mesylate, will be shared equally between the 2 companies.
The collaboration seeks to initiate additional clinical studies evaluating the efficacy and safety of the combination with pembrolizumab in 11 potential new indications in 6 cancer types, including endometrial cancer, nonsmall cell lung cancer, HCC, head and neck cancer, bladder cancer, and melanoma.
“Together with Eisai, we aim to maximize the value of Lenvima for its current indications while jointly pursuing additional approvals in combination with Keytruda across a wide range of cancers,” said Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories, in a statement. “There is strong scientific evidence supporting synergistic effects of Keytruda when used in combination with Lenvima, and the companies have already received Breakthrough Therapy designation from the US FDA for the Keytruda/Lenvima combination in renal cell carcinoma. Through this collaboration, we will both broaden our oncology portfolio and have the opportunity to help even more cancer patients around the world.”
Per the established contract, Merck will pay Eisai an upfront payment of $300 million US dollars and up to $650 million for certain option rights through March 2021. Merck is also required to pay $450 million US dollars as reimbursement for research and development expenses. Eisai could receive another $385 million US dollars in clinical and regulatory milestones and up to $3.97 billion US dollars for the achievement of milestones associated with lenvatinib mesylate sales.
The collaboration also gives Eisai access to Merck’s research and development, as well as its prominent commercial sales, as a means of maximizing the potential of lenvatinib mesylate.
Lee C, Makker V, Rasco D, et al. A phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with renal cell carcinoma. Presented at ESMO 2017 Congress; September 8-12, 2017; Madrid, Spain. Abstract 847O.