Keynote-181: Phase 3, Open-Label Study Of Second-Line Pembrolizumab Vs Single-Agent Chemotherapy In Patients With Advanced/Metastatic Esophageal Adenocarcinoma.

TPS4140Background: Tumors can hijack the PD-1 pathway to suppress immune control. Overexpression of the PD-1 ligand PD-L1 in esophageal cancer may be associated with a poor prognosis. Pembrolizumab (pembro) is a monoclonal antibody that can reinstate the antitumor autoimmune response by blocking the PD-1–ligand interaction. It demonstrated antitumor activity (ORR, 30.4%; DOR, 40 weeks) and was well tolerated in patients with PD-L1+advanced esophageal cancer (phase 1b KEYNOTE-028). The open-label, randomized, phase 3 KEYNOTE-181 trial (NCT02564263) will compare the tumor response to pembro relative to single-agent chemotherapy in previously treated advanced/metastatic (a/m) esophageal cancer. Methods: Key eligibility criteria include age ≥ 18 years, a/m adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ), measurable disease, documented PD during/after first-line therapy, ECOG PS 0-1, no active autoimmune disease or CNS metastases...