P-105 - Pembrolizumab (MK-3475) for patients with recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma: The phase 2 KEYNOTE-059...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Oesophageal Cancer
Gastric Cancer
Presenter C. Fuchs
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors C. Fuchs1, A. Ohtsu2, J. Tabernero3, E. Van Cutsem4, A. Denker5, B. Lam5, M. Koshiji6, Y.-. Bang7
  • 1Harvard Medical School, Boston/US
  • 2National Cancer Center, Kashiwashi/JP
  • 3Vall d'Hebron Institute of Oncology, Barcelona/ES
  • 4University Hospitals Leuven, Leuven/BE
  • 5Inc., Kenilworth/US
  • 6Inc., Kenilworth/
  • 7Seoul National University Hospital, Seoul/KR



Programmed death receptor 1 (PD-1) is a negative co-stimulatory receptor that downregulates immune responses; tumors frequently hijack the PD-1 pathway to suppress an immune response. Pembrolizumab is a highly selective, humanized monoclonal antibody against PD-1 that is designed to block the interaction of PD-1 with its ligands PD-L1 and PD-L2. In the phase 1 KEYNOTE-012 trial of 39 mostly heavily pretreated patients with PD-L1–positive metastatic gastric cancer, pembrolizumab 10 mg/kg every 2 weeks (Q2W) demonstrated an acceptable safety profile and promising antitumor activity (ORR of 22% per RECIST v1.1 by central review). Based on these data, the multicohort, phase 2 KEYNOTE-059 (ClinicalTrials.gov, NCT02335411) trial was initiated to further evaluate pembrolizumab in patients with advanced gastric cancer.


Eligibility requirements include age ≥18 years, recurrent or metastatic gastric or GEJ adenocarcinoma, measurable disease per RECIST v1.1 by central review, ECOG performance status 0 or 1, provision of a newly collected or archival tumor sample for PD-L1 assessment, no active autoimmune disease, no prior chemotherapy within 2 weeks of first pembrolizumab dose, and no active brain metastases (stable metastases for ≥4 weeks are permitted). PD-L1 expression will be determined by an immunohistochemistry assay (22C3 antibody) at a central laboratory. The study includes 3 cohorts. Cohort 1 will enroll up to 180 patients with any PD-L1 status who progressed on ≥2 previous chemotherapy regimens that included a fluoropyrimidine and a platinum doublet; HER2-positive patients must have received trastuzumab. Cohort 2 will enroll approximately 20 non-Asian and 20 Asian treatment-naive, HER2-negative patients with any PD-L1 status. Cohort 3 will enroll approximately 50 treatment-naive patients with HER2-negative, PD-L1–positive tumors. Patients in cohorts 1 and 3 will receive pembrolizumab 200 mg every 3 weeks (Q3W) as monotherapy. Patients in cohort 2 will receive pembrolizumab 200 mg Q3W plus infusional 5-fluorouracil or capecitabine and 6 cycles of cisplatin. Study treatment may be continued for up to 24 months or until disease progression, intolerable toxicity, or investigator decision. Discontinuation before 24 months is permitted for patients who experience complete response and have received ≥24 weeks of study treatment and ≥2 doses beyond initial response. Eligible patients may continue study therapy beyond initial RECIST-defined progression. Tumor imaging will be performed at week 9 and every 6 weeks thereafter. AEs will be collected and graded per NCI CTCAE v4.0. Response will be assessed per RECIST v1.1, as well as per RECIST v1.1 adapted to account for the unique response patterns that may be observed with immunotherapies. Overall response rate per RECIST v1.1 by central review is the primary efficacy end point for cohorts 1 and 3. Safety and tolerability of the combination is the primary end point for cohort 2. Secondary end points include progression-free survival, overall survival, disease control rate, and duration of response. Enrollment in KEYNOTE-059 was initiated in February 2015 and will continue until up to 270 patients are enrolled across all cohorts.