Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: Phase 1b results from the JAVELIN Solid Tumor trial

Hyun Cheol Chung, Hendrik Tobias Arkenau, Jeeyun Lee, Sun Young Rha, Do Youn Oh, Lucjan Wyrwicz, Yoon Koo Kang, Keun Wook Lee, Jeffrey R. Infante, Sung Sook Lee, Margaret Kemeny, Ulrich Keilholz, Bohuslav Melichar, Alain Mita, Ruth Plummer, Denis Smith, Arnold B. Gelb, Huiling Xiong, Janet Hong, Vikram ChandHoward Safran

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32 Citations (Scopus)

Abstract

Background: We evaluated the antitumor activity and safety of avelumab, a human anti-PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy. Methods: In a phase 1b expansion cohort, patients without (1 L-mn) or with (2 L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10 mg/kg intravenously every 2 weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety. Results: Overall, 150 patients were enrolled (1 L-mn, n = 90; 2 L, n = 60) and median follow-up in the 1 L-mn and 2 L subgroups was 36.0 and 33.7 months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5-13.9% and 1.8-16.2%, respectively), including complete responses in 2.2% of the 1 L-mn subgroup (n = 2). In the 1 L-mn and 2 L subgroups, median duration of response was 21.4 months (95% CI, 4.0-not estimable) and 3.5 months (95% CI, 2.8-8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1 L-mn and 2 L subgroups was 2.8 months (95% CI, 2.3-4.1) and 1.4 months (95% CI, 1.3-1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7-32.4%) and 7.9% (95% CI, 2.6-17.2%), and median OS was 11.1 months (95% CI, 8.9-13.7) and 6.6 months (95% CI, 5.4-9.4), respectively. In the 1 L-mn subgroup, median OS measured from start of 1 L chemotherapy was 18.7 months (95% CI, 15.4-20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade ≥3 TRAE, including 1 treatment-related death. Conclusion: Avelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC. Trial registration: ClinicalTrials.gov NCT01772004; registered 21 January 2013.

Original languageEnglish
Article number30
JournalJournal for ImmunoTherapy of Cancer
Volume7
Issue number1
DOIs
Publication statusPublished - 2019 Feb 4

Bibliographical note

Funding Information:
This trial was sponsored by Merck KGaA and is part of an alliance between Merck KGaA and Pfizer, Inc., New York, NY, USA. Medical writing support was provided by ClinicalThinking and was funded by Merck KGaA and Pfizer.

Publisher Copyright:
© 2019 The Author(s).

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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