KENILWORTH, N.J.–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the pivotal Phase 3 KEYNOTE-240 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, plus best supportive care, for the treatment of patients with advanced hepatocellular carcinoma (HCC) who were previously treated with systemic therapy, did not meet its co-primary endpoints of overall survival (OS) and progression-free survival (PFS) compared with placebo plus best supportive care. In the final analysis of the study, there was an improvement in OS for patients treated with KEYTRUDA compared to placebo, however these OS results did not meet statistical significance per the pre-specified statistical plan (HR=0.78 [95% CI, 0.611-0.998]; p=0.0238). Results for PFS were also directionally favorable in the KEYTRUDA arm compared with placebo but did not reach statistical significance (HR=0.78 [95% CI, 0.61-0.99]; p=0.0209). The key secondary endpoint of objective response rate (ORR) was not formally tested, since superiority was not reached for OS or PFS. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies. Results will be presented at an upcoming medical meeting and have been shared with the U.S. Food and Drug Administration for discussion.
“While we are disappointed KEYNOTE-240 did not meet its co-primary endpoints, the results for overall survival, progression-free survival and objective response rate are generally consistent with findings from the Phase 2 study, KEYNOTE-224, which led to the accelerated approval of KEYTRUDA for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We sincerely thank the patients and investigators for their participation in this study and are committed to helping patients diagnosed with this common and difficult-to-treat type of liver cancer.”
KEYTRUDA is being studied across multiple settings and lines of therapy for HCC through our broad clinical program that includes 10 clinical trials sponsored by Merck or in collaborations. As monotherapy in second-line HCC, in addition to KEYNOTE-240 and KEYNOTE-224, KEYTRUDA is being investigated in the ongoing Phase 3, KEYNOTE-394 trial, a randomized, double-blind trial evaluating KEYTRUDA in combination with best supportive care, compared to placebo in combination with best supportive care, in Asian patients with advanced HCC who were previously treated with systemic therapy. In addition, there are several ongoing trials investigating KEYTRUDA in combination with other treatments, including therapies through our collaborations.
KEYNOTE-240 is a Phase 3, randomized, double-blind trial (ClinicalTrials.gov, NCT02702401) evaluating KEYTRUDA plus best supportive care compared to placebo plus best supportive care in patients with advanced HCC who were previously treated with systemic therapy. The primary endpoints are OS and PFS. The secondary endpoints include ORR, duration of response, disease control rate and time to progression. The study enrolled 413 patients who were randomized to receive either KEYTRUDA (200 mg fixed dose 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.
About Hepatocellular Carcinoma
Hepatocellular carcinoma is the most common type of liver cancer in adults, which is the sixth most frequently diagnosed cancer worldwide. 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 frequently diagnosed at an advanced stage – has one of the highest mortality rates of solid cancers, with a five-year survival rate of less than 15 percent.
About KEYTRUDA ® (pembrolizumab) Injection, 100mg
KEYTRUDA is an anti-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 program. There are currently more than 900 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
Tuesday, February 19, 2019