Merck Initiates Phase III Trial of Pembrolizumab Plus Lenvatinib in First-Line Advanced Melanoma

By Feng Qiu

On March 10, MSD initiated a double-blind, randomized, international, multicenter Phase III trial of pembrolizumab in combination with lenvatinib for the treatment of advanced melanoma. The study aims to evaluate the efficacy and safety of pembrolizumab plus lenvatinib versus pembrolizumab plus placebo as first-line therapy in patients with advanced melanoma. The trial plans to enroll 660 participants, with 97 medical institutions worldwide participating in the study. The first patient was enrolled on March 12, 2019.

Source: Drug Clinical Trial Registration and Information Publicity Platform

The primary endpoints of this study were progression-free survival (PFS) and overall survival (OS), as assessed by blinded independent central review (BICR) according to the modified RECIST 1.1 criteria; the secondary endpoints included objective response rate (ORR) and duration of response (DOR) as assessed by BICR per the modified RECIST 1.1 criteria, safety and tolerability, mean change from baseline in quality of life and performance status scale scores, and time to deterioration (TTD) in quality of life and performance status. The study arms were as follows:

Lenvatinib is a multi-target kinase inhibitor developed by Eisai, capable of blocking a series of regulators within tumor cells, including VEGFR1-3, FGFR1-4, PDGFRα, KIT, and RET. The drug was approved for marketing in China in September 2018 for the first-line treatment of liver cancer, under the brand name Lenvima. In the 2019 national medical insurance negotiations, Eisai's lenvatinib failed to be included in the National Reimbursement Drug List. On June 3, 2019, Chia Tai Tianqing submitted a marketing application for Lenvatinib Mesylate Capsules, becoming the first domestic manufacturer to submit such an application, with approval expected in 2020.

In July 2018, pembrolizumab injection (Keytruda) was approved by the National Medical Products Administration for marketing as a second-line therapy for melanoma, becoming the second PD-1/PD-L1 inhibitor launched in China. It subsequently received approval for multiple indications in non-small cell lung cancer (NSCLC). In July 2019, Merck Sharp & Dohme and Eisai jointly announced that the U.S. FDA had granted Breakthrough Therapy Designation to the combination therapy of pembrolizumab and lenvatinib for the first-line treatment of patients with advanced unresectable hepatocellular carcinoma (HCC) who are not candidates for locoregional therapy.

Domestic Marketing Authorization Application and Approval Status of Pembrolizumab Injection