Multicohort phase II KEYNOTE-059 study of pembrolizumab (MK-3475) for recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

TPS4135 Background: Many tumors suppress immune control via the programmed death receptor 1 (PD-1) pathway. Pembrolizumab is an anti–PD-1 monoclonal antibody designed to block the interaction of PD-1 with its ligands PD-L1 and PD-L2. In 39 patients (pts) with PD-L1–positive metastatic gastric cancer enrolled in the phase I KEYNOTE-012 trial, 67% of whom had ≥ 2 prior lines of therapy, pembrolizumab 10 mg/kg every 2 wk (Q2W) provided a 22% confirmed ORR (RECIST v1.1, central review) and an acceptable safety profile. KEYNOTE-59 (NCT02335411) is an ongoing, international, 3-cohort, phase II study designed to further assess pembrolizumab in pts with gastric cancer. Methods: All cohorts of KEYNOTE-059 will enroll pts with recurrent or metastatic gastric or GEJ adenocarcinoma, ≥ 1 measurable lesion, and ECOG PS 0 or 1. All pts must provide a newly collected (preferred) or archival tumor biopsy sample for immunohistochemical determination of PD-L1 expression at a central laboratory. In cohort 1, up to 180 pts with any PD-L1 status who progressed on ≥ 2 prior chemotherapy regimens that included a fluoropyrimidine and platinum doublet and, if HER2+, trastuzumab, will receive pembrolizumab 200 mg Q3W. In cohort 2, approximately 20 non-Asian and 20 Asian treatment-naive, HER2– pts with any PD-L1 status will receive pembrolizumab 200 mg Q3W plus infusional 5-FU or capecitabine and 6 cycles of cisplatin. In cohort 3, approximately 50 treatment-naive, HER2– pts with PD-L1–positive tumors will receive pembrolizumab 200 mg Q3W. In all cohorts, pembrolizumab will be given for 24 mo or until disease progression, intolerable toxicity, or investigator decision; treatment may be discontinued for complete response. Eligible pts may continue pembrolizumab beyond initial RECIST-defined progression. AEs will be monitored. Response will be assessed at wk 9 and every 6 wk thereafter per RECIST v1.1 and RECIST adapted to account for response patterns observed with immunotherapies. Primary end point is ORR per RECIST v1.1 by central review; secondary end points include PFS, OS, disease control rate, and duration of response. KEYNOTE-059 enrollment began in February 2015. Clinical trial information: NCT02335411.