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

TPS184 Background: Pembrolizumab (pembro) is a humanized monoclonal antibody that targets the PD-1 receptor and prevents it from interacting with its ligands, PD-L1 and PD-L2. In the phase I KEYNOTE-012 trial, pembro showed an acceptable safety profile and promising antitumor activity in patients (pts) with PD-L1+ metastatic gastric cancer. The multicohort, phase II KEYNOTE-059 (NCT02335411) trial was designed to further evaluate pembro as monotherapy or in combination with 5-fluorouracil (5-FU) and cisplatin in pts with advanced gastric cancer. Methods: Patients ≥ 18 y who have relapsed or metastatic gastric or GEJ adenocarcinoma, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior chemotherapy within 2 wk of the first dose of pembro are eligible. PD-L1 expression status will be determined by IHC using the 22C3 antibody (Merck). In cohort 1 (C1), up to 180 pts with any PD-L1 status whose disease progressed on ≥ 2 prior chemotherapy regimens, including a fluoropyrimidine and platinum doublet and, if HER2+, trastuzumab, will receive pembro 200 mg Q3W. In cohort 2 (C2), ~12 Asian and ~6 non-Asian, treatment-naive, HER2– pts of any PD-L1 status will receive pembro 200 mg Q3W + infusional 5-FU or capecitabine and 6 cycles of cisplatin. In cohort 3 (C3), ~25 treatment-naive pts with HER2–/PD-L1+ tumors will receive pembro 200 mg Q3W. Treatment may continue for up to 24 mo or until progression, intolerable toxicity, or investigator decision. Response will be assessed at wk 9 and every 6 wk thereafter per RECIST v1.1 and RECIST v1.1 adapted for immunotherapy response patterns. Treatment may be discontinued for eligible pts who have a CR. Eligible pts may continue treatment beyond initial RECIST-defined progression. AEs will be collected throughout the study and for 30 d thereafter (90 d for serious AEs) and graded per NCI CTCAE v4.0. The primary efficacy end point for C1 and C3 is ORR per RECIST v1.1 by central review; the primary end point for C2 is safety and tolerability of the combination. Secondary end points include PFS, OS, DCR, and duration of response. Enrollment in KEYNOTE-059 is ongoing and will continue until up to 223 pts are enrolled across all cohorts. Clinical trial information: NCT02335411.