FDA Grants Priority Review to Keytruda for Advanced Liver Cancer

The Food and Drug Administration (FDA) granted a priority review to Keytruda (pembrolizumab) for the treatment of previously treated patients with advanced hepatocellular carcinoma (HCC), according to Merck, the manufacturer of the anti-PD-1 therapy.

“There continues to be a significant need for new options in the treatment of advanced hepatocellular carcinoma, which is the most common type of liver cancer,” Scot Ebbinghaus, M.D., vice president of clinical research at Merck Research Laboratories, said in a statement.

“The data supporting our application provide a clear rationale for the advancement of the Keytruda clinical program for hepatocellular carcinoma, and we are grateful for the opportunity to work with the FDA to potentially bring Keytruda to patients living with this difficult-to-treat cancer,” he added.

The new supplemental Biologics License Application, which seeks accelerated approval for this new indication, is based on data from the non-randomized, multicenter, open-label phase 2 Keynote-224 trial — designed to evaluate the efficacy and safety of Keytruda in 169 patients with advanced HCC, of whom 104 eligible patients were enrolled and treated.

Patients received 200 mg of Keytruda intravenously every three weeks for about two years or until disease progression, unacceptable toxicity, patient withdrawal or investigator decision.

Objective response rates (ORR), which was defined as the proportion of patients with complete or partial response in all who received at least one dose of Keytruda, served as the primary endpoint.

Results from the trial were recently presented at the 2018 American Society of Clinical Oncology Annual Meeting and published simultaneously in The Lancet Oncology.

Patients treated with Keytruda achieved an ORR of 17 percent.

Best overall responses included one complete (1 percent) and 17 partial (16 percent) responses, as well as 46 patients (44 percent) who experienced stable disease and 34 (33 percent) with progressive disease. Six patients (6 percent) did not have a post-baseline assessment on the cutoff date and were considered not to be assessable.

In total, 76 patients (73 percent) experienced treatment-related side effects, which were serious in 16 patients (15 percent). Grade 3 treatment-related side effects occurred in 25 patients (24 percent), which included increased aspartate aminotransferase concentration (AST; 7 percent), increased alanine aminotransferase concentration (ALT; 4 percent) and fatigue (4 percent). One patient experienced grade 4 hyperbilirubinaemia, and one death occurred from ulcerative oesophagitis attributed to treatment.

“These results indicate that pembrolizumab might be a treatment option for these patients,” the researchers wrote in the abstract. “This drug is undergoing further assessment in two phase 3, randomized trials as a second-line treatment in patients with hepatocellular carcinoma.”

The agency is set to make its decision by Nov. 9, 2018.