Merck's Keytruda Nominated for Priority Review in China for Sixth Indication, Likely First-Line Advanced Hepatocellular Carcinoma

Source | Medical Perspective

Latest Public Notice from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration: The New Drug Application (NDA) for Merck Sharp & Dohme’s (MSD) blockbuster PD-1 inhibitor Keytruda (pembrolizumab) is proposed for priority review, on the grounds that it meets the criteria for conditional approval. According to the CDE website, this is the sixth marketing application submitted for Keytruda in China. Based on the progress of ongoing clinical trials and industry trends, the indication is likely first-line treatment for advanced hepatocellular carcinoma (HCC). Previously, Keytruda has been approved in China for five indications, including melanoma and non-small cell lung cancer (NSCLC).

Source: CDE Official Website

Since its initial approval for marketing in China in July 2018, Keytruda has received approval for a total of five indications in China to date. These are: first-line treatment of metastatic melanoma; first-line treatment of EGFR-negative and ALK-negative metastatic non-squamous non-small cell lung cancer (NSCLC); first-line treatment of locally advanced or metastatic NSCLC with positive PD-L1 expression and no specific genetic mutations; first-line treatment of metastatic squamous NSCLC; and the fifth indication, which may be for the second-line treatment of esophageal cancer.

According to the Drug Clinical Trial Registration and Information Publicity Platform, Keytruda has registered a total of 31 clinical trials in China. The majority are international multicenter studies, with 27 of them being Phase III trials. In addition to approved indications, Phase III clinical trials are underway for hepatocellular carcinoma (HCC), gastric cancer, breast cancer, gastroesophageal junction adenocarcinoma, cervical cancer, prostate cancer, urothelial carcinoma, biliary tract cancer, and endometrial cancer. Among these, the most advanced programs include Keytruda combined with lenvatinib or as monotherapy for first-line treatment of advanced HCC, and Keytruda combined with chemotherapy for first-line treatment of advanced esophageal cancer.

The new marketing application for Keytruda is proposed for inclusion in the priority review program, with the potential indication being first-line treatment for advanced hepatocellular carcinoma (HCC). According to the 2020 edition of the “Guidelines for Diagnosis and Treatment of Primary Liver Cancer” recently released by the Chinese Society of Clinical Oncology (CSCO), the combination of Keytruda and the oral multi-receptor tyrosine kinase inhibitor lenvatinib has received a Grade III expert recommendation (Category 2B evidence) for first-line treatment of advanced HCC.

Previously, this combination therapy demonstrated positive results in a Phase 1b trial named KEYNOTE-524/study116, achieving a clinically meaningful overall response rate (ORR) in patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic treatment. The combination therapy achieved an ORR of 36%, with a median duration of response (DOR) of 12.6 months.

Currently, Keytruda has been approved in multiple countries and regions worldwide, with indications spanning more than ten cancer types. It has also received two tumor-agnostic approvals in the United States: one for the treatment of MSI-H or dMMR solid tumors, and another for monotherapy in patients with unresectable or metastatic solid tumors characterized by high tumor mutational burden (TMB-H) who have experienced disease progression following prior treatments.

Based on the clinical trials currently under application and underway in China, Keytruda is expected to expand into additional indications, potentially bringing “tumor-agnostic” innovative therapies to Chinese patients.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Jul 28, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

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