Pembrolizumab (MK-3475) for previously treated metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: Phase II KEYNOTE-180 study.

TPS189 Background: PD-L1 is frequently overexpressed in esophageal cancer. Pembrolizumab is a humanized monoclonal antibody that targets the PD-1 receptor and blocks interaction with PD-L1 and PD-L2. In the multicohort, phase Ib KEYNOTE-028 trial, pembrolizumab showed manageable toxicity, a 30.4% ORR, and median duration of response of 40 wk in 23 patients (pts) with PD-L1 + advanced esophageal cancer. The single-arm, multicenter phase II KEYNOTE-180 trial is designed to further evaluate pembrolizumab as a monotherapy in pts with previously treated advanced/metastatic esophageal cancer. Methods: Key eligibility criteria include age ≥ 18 y, advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction (EGJ), measurable disease, documented progression during or after 2 prior lines of therapy, ECOG PS 0-1, no active autoimmune disease or brain metastases, and provision of a tumor sample for retrospective biomarker analysis. Pts with metastatic Siewert type I EGJ adenocarcinoma must have known HER2 status and, if HER2 + , must have documented progression on treatment containing trastuzumab. Eligible pts will receive pembrolizumab 200 mg Q3W for 35 cycles (~2 y) or until progression, unacceptable toxicity, or investigator or pt decision. Response will be assessed every 9 wk per RECIST v1.1 and RECIST adapted for immunotherapy response patterns. Treatment may be discontinued for pts who have a CR, and eligible pts may continue treatment beyond initial RECIST-defined progression. AEs will be assessed throughout treatment and for 30 d thereafter (up to 90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts will be followed for survival every 9 wk. The primary efficacy end point is ORR per RECIST v1.1 by central review. Secondary end points include PFS, OS, and duration of response. Exploratory analyses include evaluation of immune-related gene expression profiles and PD-L1 expression status as predictors of pembrolizumab efficacy. Enrollment in KEYNOTE-180 is expected to begin in October 2015 and will continue until approximately 100 pts are enrolled.