Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

Cancer. 2018 May 1;124(9):2010-2017. doi: 10.1002/cncr.31293. Epub 2018 Feb 22.


Background: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy.

Methods: Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti-PD-L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment-related AEs (TRAEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). In post hoc analyses, immune-related AEs (irAEs) were identified via an expanded AE list and medical review, and infusion-related reactions (IRRs) occurring ≤2 days after infusion and symptoms occurring ≤1 day after infusion and resolving ≤2 days after onset were identified based on prespecified Medical Dictionary for Regulatory Activities (MedDRA) terms.

Results: Of the 1738 patients analyzed, grade ≥3 TRAEs occurred in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10 patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in 4 patients (0.2%). Grade ≥3 irAEs occurred in 39 patients (2.2%) and led to discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439 patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]). An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to discontinuation in 35 patients (2.0%).

Conclusions: Avelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade ≥3 TRAEs or irAEs, and discontinuation was uncommon. IRRs occurred mainly at the time of first infusion, and repeated events were infrequent. Cancer 2018;124:2010-7. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Keywords: JAVELIN; avelumab; immunotherapy; programmed death-ligand 1 (PD-L1); safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Fatigue / chemically induced
  • Fatigue / epidemiology*
  • Fatigue / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Infusions, Intravenous / adverse effects
  • Injection Site Reaction / epidemiology*
  • Injection Site Reaction / immunology
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • avelumab