LBA-04 - Clinical outcomes and their correlation with gene expression in patients with advanced gastric cancer treated with pembrolizumab (MK-3475): KEYNOTE-...

Date 04 July 2015
Event WorldGI 2015
Session Oral and LBA abstracts
Topics Gastric Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Y-J. Bang
Citation Annals of Oncology (2015) 26 (suppl_4): 117-122. 10.1093/annonc/mdv262
Authors Y. Bang1, S. Gupta2, M. Koshiji3, K. Muro4, H.C. Chung5, V. Shankaran6, R. Geva7, D. Catenacci8, J.P. Eder9, R. Berger10, K. Emancipator11, K. Pathiraja11, T. McClanahan11, M. Ayers11, J. Lunceford11, J. Cheng11
  • 1Seoul National University Hospital, Seoul/KR
  • 2Tampa, Florida/
  • 3Kenilworth, New Jersey/
  • 4Aichi Cancer Center Hospital, Nagoya/JP
  • 5Yonsei University College of Medicine, Seoul/KR
  • 6Seattle/US
  • 7Tel-Aviv Sourasky Medical Center, Tel Aviv/IL
  • 8Chicago/US
  • 9New Haven/US
  • 10Sheba Medical Center, Tel Hashomer/IL
  • 11Kenilworth/US



PD-1 is a negative costimulatory receptor expressed on the surface of activated T cells. PD-1 binds to its ligands, PD-L1 and PD-L2, and inhibits effector T-cell function. Tumors, including gastric cancer, frequently overexpress PD-L1, and thereby suppress antitumor immunity. Pembrolizumab is a humanized monoclonal antibody against PD-1 that has demonstrated antitumor activity and a manageable safety profile in several advanced cancers. In the phase 1b KEYNOTE-012 study (NCT01848834), we previously showed that pembrolizumab provides robust antitumor activity and manageable toxicity in advanced gastric cancer. Here, we provide results for patients enrolled in Asia-Pacific (AP) and the rest of the world (ROW), and results from prespecified exploratory analyses of the relationship between immune-related gene expression signatures and outcomes.


Key eligibility criteria were recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction, ECOG PS of 0-1, measurable disease per RECIST v1.1, and PD-L1 expression in ≥1% of cells in tumor nests or distinctive stromal staining using a prototype IHC assay with the 22C3 antibody. An equal number of patients from AP and ROW were to be enrolled. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until confirmed disease progression or unacceptable toxicity. Response was assessed every 8 weeks per RECIST v1.1 by central review. The relationship between clinical outcomes and 4 prespecified RNA-based immune-related gene expression signatures that were constructed based on analyses of melanoma tumor samples and measured by the NanoString nCounter system was also assessed.


Overall, 39 patients enrolled (n = 19 from AP, n = 20 from ROW). ORR was 22% (95% CI, 10-39) overall (23% [95% CI, 7-50] for AP and 21% [95% CI, 6-46] for ROW), with a median response duration of 40 weeks (range, 20+ to 48+). 6-month PFS rate was 26% in all patients (23% and 28% for AP and ROW, respectively). 6-month OS rate was 66% in all patients (63% and 70% for AP and ROW, respectively). Treatment-related grade 3-4 AEs were observed in 13% of patients and included fatigue, hypothyroidism, pneumonitis, pemphigoid, and peripheral sensory neuropathy. Relationships between the 6-gene IFN-ɣ, 13-gene TCR signaling, 18-gene expanded immune, and 33-gene de novo gene expression signatures and ORR and PFS were observed.


Pembrolizumab provided durable antitumor activity with a manageable toxicity profile in PD-L1–positive advanced gastric cancer, with similar efficacy in patients from AP and ROW. Data suggest there is an association between efficacy and immune-related gene expression signatures. The use of gene expression information may provide an additional means of identifying those patients most likely to respond to pembrolizumab.