Merck’s phase 3 KEYNOTE-394 trial of Keytruda meets primary endpoint of OS in patients with advanced HCC previously treated with sorafenib

Merck, known as MSD outside the United States and Canada, announced that the phase 3 KEYNOTE-394 trial investigating Keytruda, Merck’s anti-PD-1 therapy, in Asian patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib met its primary endpoint of overall survival (OS).

The study found that treatment with Keytruda plus best supportive care resulted in a statistically significant improvement in OS compared with placebo plus best supportive care. KEYNOTE-394 also met its key secondary endpoints of progression-free survival (PFS) and objective response rate (ORR), with statistically significant improvements for Keytruda compared with placebo. No new safety signals were observed. These results will be presented at an upcoming medical meeting.

“Frequently diagnosed at an advanced stage, hepatocellular carcinoma has one of the highest mortality rates of solid cancers. Despite recent progress, there remains an unmet need for anti-PD-1 monotherapy after sorafenib, where Keytruda is an established treatment option for patients,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “It is very encouraging that Keytruda significantly improved overall survival in this study, and we look forward to engaging with regulatory authorities as quickly as possible.”

Keytruda was granted accelerated approval in November 2018 for the treatment of patients with HCC who have been previously treated with sorafenib, based on ORR and durability of response data from KEYNOTE-224. A subsequent study, KEYNOTE-240, did not meet its dual primary endpoints of OS and PFS. This accelerated approval for Keytruda was discussed during the FDA’s Oncologic Drugs Advisory Committee (ODAC) meeting on April 29, 2021 that voted 8-0 in favor of maintaining accelerated approval of Keytruda for this indication. KEYNOTE-394 was discussed at the ODAC meeting as a potential confirmatory trial that could verify the clinical benefit of Keytruda for these patients.

Merck is dedicated to advancing research in HCC and has a global development program of seven clinical trials that have enrolled or are expected to enroll approximately 3,000 patients. In HCC, Keytruda is being studied across multiple settings and lines of therapy as monotherapy and in combination with other treatments, including therapies through our collaborations.

KEYNOTE-394 is a randomized, double-blind, phase 3 trial (, NCT03062358) evaluating Keytruda plus best supportive care versus placebo plus best supportive care in Asian patients with advanced HCC previously treated with sorafenib or oxaliplatin chemotherapy. The primary endpoint is OS and secondary endpoints include PFS, ORR, duration of response and disease control rate. The study enrolled 453 patients who were randomized to receive either Keytruda (intravenously every three weeks for up to 35 cycles of treatment [up to approximately two years]) plus best supportive care (including pain management and management of other potential complications including ascites per local standards of care) or placebo plus best supportive care.

Hepatocellular carcinoma is the most common form of primary liver cancer, which is the sixth most frequently diagnosed cancer worldwide. It is estimated there were more than 905,000 new cases of liver cancer and more than 830,100 deaths from the disease globally in 2020, making it one of the leading causes of cancer deaths around the world. In the US, it is estimated there will be more than 42,200 new cases of liver cancer and nearly 30,300 deaths from this disease in 2021. Risk factors for liver cancer include gender, ethnicity, chronic viral hepatitis (Hep-B or Hep-C) infection, cirrhosis, alcohol use and metabolic syndrome. Hepatocellular carcinoma, which is often diagnosed at an advanced stage, has a five-year survival rate of less than 15%.

Keytruda is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research programme. There are currently more than 1,600 trials studying Keytruda across a wide variety of cancers and treatment settings. The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.



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