LBA15 - A phase 1b study of pembrolizumab (Pembro; MK-3475) in patients (Pts) with advanced gastric cancer

Date 28 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, non-colorectal
Topics Gastric Cancer
Cancer Immunology and Immunotherapy
Presenter Kei Muro
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors K. Muro1, Y. Bang2, V. Shankaran3, R. Geva4, D.V.T. Catenacci5, S. Gupta6, J.P. Eder7, R. Berger8, E.J. Gonzalez9, J. Pulini10, A.B. Ray11, M. Dolled-Filhart12, K. Emancipator13, K. Pathiraja14, X. Shu15, M.R. Koshiji16, J.D. Cheng17, H.C. Chung18
  • 1Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 2Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 3Medical Oncology, University of Washinton, Seattle/US
  • 4Oncology, Tel-Aviv Sourasky Medical Center, Tel Aviv/IL
  • 5Department Of Medicine, University of Chicago, Chicago/US
  • 6Medical Oncology, H.Lee Moffitt Cancer Center and Research Institute, Tampa/US
  • 7Medical Oncology, Yale University, New Haven/US
  • 8Oncology And Radiotherapy, Sheba Medical Center, Tel Hashomer/IL
  • 9Clinical Development Execution Organization – Oncology, Merck & Co., Inc., Rahway/US
  • 10Clinical Development Execution Organization, Merck & Co., Inc., North Wales/US
  • 11Oncology, Merck & Co., Inc., Rahway/US
  • 12Molecular Biomarkers And Diagnostics, Merck & Co., Inc., Rahway/US
  • 13Molecular Biomarkers And Diagnostics, Merck Research Laboratories, Rahway/US
  • 14Bards, Merck & Co., Inc., Rahway/US
  • 15Bards, Merck & Co., Inc., North Wales/US
  • 16Clinical Oncology, Merck & Co., Inc., Rahway/US
  • 17Clinical Oncology, Merck & Co., Inc., North Wales/US
  • 18Medical Oncology, Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR

 

Abstract

Aim

The PD-1 receptor-ligand pathway can be used by tumors to evade immune surveillance, thereby allowing neoplastic growth. Pembro is a highly selective, humanized IgG4/kappa isotype monoclonal antibody designed to block PD-1 interaction with its ligands PD-L1 and PD-L2, thus reactivating the immune system to eradicate the host tumor. In a phase 1b study (Clinicaltrials.gov: NCT01848834), we assessed the safety, tolerability, and antitumor activity of pembro in gastric cancer pts.

Methods

Using a prototype immunohistochemistry assay, PD-L1 expression was assessed in archival tumor samples from pts with recurrent/metastatic adenocarcinoma of the stomach or gastroesophageal junction. Eligible pts with PD-L1 staining in stroma or ≥1% of tumor cells were enrolled and treated with pembro 10 mg/kg every 2 weeks for up to 24 months or until complete response, disease progression, or unacceptable toxicity. Enrollment was designed to include an equal number of pts from Asia Pacific (AP) and the rest of the world (ROW). Adverse events (AEs) were monitored and graded per the NCI CTCAE v4.0. Radiographic imaging was performed every 8 weeks. Primary efficacy end point was overall response rate (ORR) assessed by RECIST v1.1.

Results

Of the 162 pts screened, 65 (40%) were PD-L1+ and 39 enrolled: 19 from AP, 20 from ROW. Median age was 63 y, and 72% of pts were men. Pts from AP were more heavily pretreated than pts from ROW (≥2 prior therapies in 79% vs 55%). Median follow-up duration was ∼6 mo. The most common AEs deemed treatment related by investigators were hypothyroidism and fatigue (n = 5 each). Grade ≥3 AEs deemed treatment related occurred in 3 pts (n = 1 each for hypoxia, peripheral neuropathy, and pneumonitis). ORR (confirmed + unconfirmed) was 32% in AP and 30% in ROW. Responses were ongoing for 6/6 AP pts and 5/6 ROW pts (median response duration not reached; range 8+ to 20+ wk). Evidence of an association between PD-L1 expression and PFS (P = 0.032) and ORR (P = 0.071) was observed.

Conclusions

Pembro was generally well tolerated by and provided antitumor activity in pts with advanced gastric cancer that expressed PD-L1. The robust antitumor activity observed supports the further development of pembro in advanced gastric cancer.

Disclosure

E.J. Gonzalez: Is employee of and holds stock in Merck & Co., Inc.; J. Pulini: Is former employee of Merck & Co., Inc.; A.B. Ray, M. Dolled-Filhart, K. Emancipator, K. Pathiraja, X. Shu and M.R. Koshiji: Is an employee of Merck & Co., Inc.; J. Cheng: Is an employee of and holds stock in Merck & Co., Inc. All other authors have declared no conflicts of interest.