FDA Approves Pembrolizumab for Patients With HER2-Positive, PD-L1 Expressing Gastric or Gastroesophageal Junction Adenocarcinoma

On March 19th, 2025, the US Food and Drug Administration (FDA) approved first-line pembrolizumab plus trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy for patients with locally advanced, unresectable, or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma with PD-L1 expression. This approval was based on results from the KEYNOTE-811 study. 

In this multi-center, double-blind, placebo-controlled trial, researchers enrolled 698 patients with HER2-positive advanced G/GEJ adenocarcinoma who did not receive prior systemic therapy for metastatic disease including PD-L1 expressing patients with a CPS ≥ 1 (n = 594). Patients were randomized on a 1-to-1 basis to receive either 200 mg of pembrolizumab or placebo plus trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin. Primary end points included progression-free survival (PFS) and overall survival (OS). Key secondary end points included overall response rate (ORR) and duration of response. 

At analysis, statistically significant OS and PFS improvement was observed in patients in the pembrolizumab arm. Among patients with PD-L1 expressing tumors, median PFS was 10.9 months in the pembrolizumab arm and 7.3 months in the placebo arm. Median OS was 20.1 months and 15.7 months, respectively. The ORR was 73% in the pembrolizumab arm and 58% in the placebo arm. The median duration of response was 11.3 months and 9.6 months, respectively. Safety was consistent with prior studies. 

The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks plus trastuzumab and chemotherapy. 

Source: 

FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1). Accessed on March 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-her2-positive-gastric-or-gastroesophageal-junction-adenocarcinoma