231TiP KEYNOTE-059: Phase 2 study of pembrolizumab (MK-3475) for recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma

Abstract

Background: Pembrolizumab (pembro) is a humanized monoclonal antibody against PD-1 that prevents it from interacting with its ligands, PD-L1 and PD-L2. In the phase 1 KEYNOTE-012 trial of patients ( pts) with PD-L1+ metastatic gastric cancer, pembro showed an acceptable safety profile and promising antitumor activity. The multicohort, phase 2 KEYNOTE-059 (NCT02335411) trial was designed to further evaluate pembro in pts with advanced gastric cancer. Trial design: Key eligibility criteria are age ≥18 y, relapsed or metastatic gastric or gastroesophageal junction adenocarcinoma, measurable disease, ECOG PS 0-1, no active autoimmune disease, no prior chemotherapy within 2 wk of first dose, and no active brain metastases. PD-L1 status will be assessed in all pts via IHC. Cohort 1 (C1) will include up to 180 pts with any PD-L1 status who progressed on ≥2 prior chemotherapy regimens that included a fluoropyrimidine and a platinum doublet; HER2+ pts must have received trastuzumab. Cohort 2 (C2) will enroll ∼12 Asian and ∼6 non-Asian, treatment-naive, HER2- pts of any PD-L1 status. Cohort 3 (C3) will include ∼25 treatment-naive pts with HER2-/PD-L1+ tumors. In C1 and C3, pts will receive pembro 200 mg Q3W. In C2, pts will receive pembro 200 mg Q3W + infusional 5-FU or capecitabine and 6 cycles of cisplatin. Treatment may continue for up to 24 mo or until progression, intolerable toxicity, or investigator decision. Discontinuation before 24 mo is permitted for pts who have CR and receive ≥24 wk of treatment and ≥2 doses beyond initial response. Eligible pts may continue treatment beyond initial RECIST-defined progression. AEs will be collected and graded per NCI CTCAE v4.0. Response will be assessed at wk 9 and every 6 wk thereafter per RECIST v1.1 and RECIST v1.1 adapted to account for the unique response patterns that may be observed with immunotherapy. ORR per RECIST v1.1 by central review is the primary efficacy end point for C1 and C3; safety and tolerability of the combination is the primary end point for C2. Secondary end points include PFS, OS, DCR, and duration of response. Enrollment in KEYNOTE-059 was initiated in February 2015 and will continue until up to 270 pts are enrolled across all cohorts.