After consulting with the Food and Drug Administration (FDA), Merck is voluntarily withdrawing the US indication for Keytruda® (pembrolizumab) for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (combined positive score [CPS ≥1]) as determined by an FDA-approved test, with disease progression on or after 2 or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, human epidermal growth factor receptor 2 (HER2)/neu-targeted therapy.
In September 2017, the FDA granted accelerated approval to Keytruda for recurrent locally advanced or metastatic gastric or GEJ adenocarcinoma based on tumor response rate and durability of response data from the phase 2 KEYNOTE-059 (ClinicalTrials.gov Identifier: NCT02335411). However, results from a subsequent confirmatory phase 3 trial showed that treatment with Keytruda did not meet the postmarketing requirement for overall survival benefit.
The decision to withdraw the indication does not affect other approved indications for Keytruda. Patients who are receiving treatment with Keytruda for metastatic gastric cancer in the third- or further-line setting should consult with their health care provider.
“While there remains an unmet need for heavily pre-treated patients with advanced gastric cancer, we recognize that the treatment landscape has evolved and we respect the FDA’s efforts to continually evaluate accelerated approvals,” said Dr Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “Our research with Keytruda has contributed to recent advances in the treatment of gastric cancer, and we are continuing to advance studies to help more patients with this disease.”
According to the FDA’s accelerated approval program, a drug may be approved earlier if it is intended to treat a serious condition or fills an unmet need; the approval is based on a surrogate end point that is thought to predict clinical benefit. A confirmatory trial is then required to prove clinical benefit. If the confirmatory trial does not show clinical benefit, the Agency can take steps to remove the drug or indication.
Merck provides update on Keytruda® (pembrolizumab) indication in third-line gastric cancer in the US. [press release]. Kenilworth, NJ: Merck; July 1, 2021.