FDA Grants Priority Review to Pembrolizumab Plus Chemo for Advanced Esophageal or GEJ Cancer

The FDA has accepted and granted priority review for a new supplemental biologics license application (sBLA) for pembrolizumab (Keytruda) in combination with platinum and fluoropyrimidine based chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the esophagus and gastroesophageal junction (GEJ), according to Merck, the developer of the anti-PD-1 therapy.

The FDA has set a prescription drug user fee act (PDUFA) target action date of April 13, 2021.

The sBLA is supported by data from the pivotal phase 3 KEYNOTE-590 trial, in which pembrolizumab plus chemotherapy demonstrated significant improvements in the dual primary end points of overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with locally advanced unresectable or metastatic esophageal and GEJ cancer, regardless of PD-L1 expression status and tumor histology. Data from KEYNOTE-590 were presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“Patients with newly diagnosed esophageal and GEJ cancer face an aggressive disease with a poor prognosis, despite the currently available treatment options,” said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. “We look forward to working with the FDA to bring a new option to patients in the first-line setting.”

In the phase 3, randomized, double-blind trial, researchers evaluated pembrolizumab in combination with platinum and fluoropyrimidine based chemotherapy versus placebo plus chemotherapy (cisplatin plus 5-fluorouracil [5-FU]) for the first-line treatment of patients with locally advanced unresectable or metastatic esophageal and GEJ cancer. In addition to the primary end points, key secondary end points included objective response rate and duration of response.

A total of 749 patients were enrolled in the study and randomized to receive either:

• pembrolizumab at a dose of 200 mg intravenously [IV] on day 1 of each 3-week cycle for up to 35 cycles; plus cisplatin at a dose of 80 mg/m2 IV on day 1 of each 3-week cycle for up to 6 cycles; plus 5-FU at a dose of 800 mg/m2 IV per day on day 1 to day 5 of each 3-week cycle, or per local standard for 5-FU administration, for up to 35 cycles; or
• placebo; plus cisplatin at a dose of 80 mg/m2 IV on day 1 of each 3-week cycle for up to 6 cycles); plus 5-FU at a dose of 800 mg/m2 IV per day on day 1 to day 5 of each 3-week cycle, or per local standard for 5-FU administration, for up to 35 cycles.

Currently, pembrolizumab is approved in the US, China, and Japan as monotherapy for the second-line treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10). However, Merck indicated it is continuing to study pembrolizumab across a variety of settings and stages of gastrointestinal cancer, including gastric, hepatobiliary, esophageal, pancreatic, colorectal and anal cancers, through its broad clinical program.

Reference:

FDA Grants Priority Review to Merck’s Supplemental Biologics License Application for KEYTRUDA® (pembrolizumab) Plus Chemotherapy as First-Line Treatment for Locally Advanced Unresectable or Metastatic Esophageal and Gastroesophageal Junction Cancer [news release]. Kenilworth, NJ. Published December 17, 2020. Accessed December 17, 2020. https://www.businesswire.com/news/home/20201217005083/en/FDA-Grants-Priority-Review-to-Merck%E2%80%99s-Supplemental-Biologics-License-Application-for-KEYTRUDA%C2%AE-pembrolizumab-Plus-Chemotherapy-as-First-Line-Treatment-for-Locally-Advanced-Unresectable-or-Metastatic-Esophageal-and-Gastroesophageal-Junction-Cancer