title: Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial.
abstract: BACKGROUND
  Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer. As part of the phase 1b KEYNOTE-012 study, we aimed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction.
  
  
  METHODS
  This study was a multicentre, open-label, phase 1b trial done at 13 cancer research centres in the USA, Israel, Japan, South Korea, and Taiwan. We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred. Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan. The study is registered with ClinicalTrials.gov, number NCT01848834, and is ongoing but no longer enrolling patients.
  
  
  RESULTS
  From Oct 23, 2013, to May 5, 2014, 39 patients were enrolled. 36 were evaluable for response by central assessment. Eight (22%, 95% CI 10-39) patients were judged to have had an overall response at central review; all responses were partial. All 39 patients were included in the safety analyses. Five (13%) patients had a total of six grade 3 or 4 treatment-related adverse events, consisting of two cases of grade 3 fatigue, one case each of grade 3 pemphigoid, grade 3 hypothyroidism, and grade 3 peripheral sensory neuropathy, and one case of grade 4 pneumonitis. No treatment-related deaths occurred.
  
  
  CONCLUSIONS
  In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials.
  
  
  BACKGROUND
  Merck & Co.
authors.affiliation: Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address: kmuro@aichi-cc.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.affiliation: Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Shankaran
authors.affiliation: Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Ravit
authors.initials: R
authors.lastname: Geva
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Catenacci
authors.affiliation: University of Minnesota, Minneapolis, MN, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Yale University, New Haven, CT, USA.
authors.forename: Joseph Paul
authors.initials: JP
authors.lastname: Eder
authors.affiliation: Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Talia
authors.initials: T
authors.lastname: Golan
authors.affiliation: Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Dung T
authors.initials: DT
authors.lastname: Le
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Burtness
authors.affiliation: University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
authors.forename: Autumn J
authors.initials: AJ
authors.lastname: McRee
authors.affiliation: National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Merck & Co, Kenilworth, NJ, USA.
authors.forename: Kumudu
authors.initials: K
authors.lastname: Pathiraja
authors.affiliation: Merck & Co, Kenilworth, NJ, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Lunceford
authors.affiliation: Merck & Co, Kenilworth, NJ, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Emancipator
authors.affiliation: Merck & Co, Kenilworth, NJ, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Juco
authors.affiliation: Merck & Co, Kenilworth, NJ, USA.
authors.forename: Minori
authors.initials: M
authors.lastname: Koshiji
authors.affiliation: Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C582435:pembrolizumab