FDA Grants Priority Review to Pembrolizumab for Advanced Hepatocellular Carcinoma

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

The agency is set to make its decision on the new supplemental Biologics License Application by Nov. 9, 2018.

“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, MD, 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 application is based on data from the non-randomized, multicenter open-label phase II Keynote-224 trial — designed to evaluate the efficacy and safety of pembrolizumab in 169 patients with advanced HCC, of whom 104 eligible patients were enrolled and treated.

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 received 200 mg of pembrolizumab intravenously every 3 weeks for about 2 years or until disease progression, unacceptable toxicity, patient withdrawal, or investigator decision.

Objective response rates (ORR) served as the primary endpoint. Patients treated with pembrolizumab achieved an ORR of 17% (n = 18; 95% CI, 11—26).

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

In total, 76 patients (73%) experienced treatment-related adverse events (TRAEs), which were serious in 16 (15%) patients. Grade 3 TRAEs occurred in 25 patients (24%), which included increased aspartate aminotransferase concentration (AST; 7%), increased alanine aminotransferase concentration (ALT; 4 %), and fatigue (4%). One patient experienced grade 4 hyperbilirubinaemia, and 1 death occurred from ulcerative oesophagitis attributed to treatment.