KEYNOTE-859: a Phase III study of pembrolizumab plus chemotherapy in gastric/gastroesophageal junction adenocarcinoma

Josep Tabernero, Yung-Jue Bang, Eric Van Cutsem, Charles S Fuchs, Yelena Yuriy Janjigian, Pooja Bhagia, Kan Li, David Adelberg, Shu Kui Qin, Josep Tabernero, Yung-Jue Bang, Eric Van Cutsem, Charles S Fuchs, Yelena Yuriy Janjigian, Pooja Bhagia, Kan Li, David Adelberg, Shu Kui Qin

Abstract

Current guidelines recommend two-drug cytotoxic chemotherapy with a fluoropyrimidine (fluorouracil or capecitabine) and a platinum-based agent (oxaliplatin or cisplatin) as first-line treatment for advanced gastric cancer. Pembrolizumab monotherapy has demonstrated durable antitumor activity in patients with advanced programmed death ligand 1-positive (combined positive score ≥1) gastric/gastroesophageal junction adenocarcinoma. Accumulating evidence indicates that combining pembrolizumab with standard-of-care chemotherapy for the treatment of advanced or metastatic cancer improves clinical outcomes. We describe the rationale for and the design of the randomized, double-blind, placebo-controlled, Phase III KEYNOTE-859 study, which is investigating pembrolizumab in combination with chemotherapy as first-line treatment for patients with human epidermal growth factor receptor 2-negative advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma. The planned sample size is 1542 patients, and the primary end point is overall survival. Clinical trial registration: NCT03675737 (ClinicalTrials.gov).

Keywords: HER2-negative; adenocarcinoma; chemotherapy; first-line therapy; gastric cancer; gastroesophageal junction cancer; immunotherapy; pembrolizumab.

Figures

Figure 1.. KEYNOTE-859 study design.
Figure 1.. KEYNOTE-859 study design.
CAPOX: Capecitabine plus oxaliplatin; CPS: Combined positive score; ECOG PS: Eastern Cooperative Oncology Group performance status; FP: 5-Fluorouracil plus cisplatin; GEJ: Gastroesophageal junction; iv.: Intravenously; Q3W: Every 3 weeks.

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