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

Karen Kelly, Jeffrey R. Infante, Matthew H. Taylor, Manish R. Patel, Deborah J. Wong, Nicholas Iannotti, Janice M. Mehnert, Anja H. Loos, Helga Koch, Isabell Speit, James L. Gulley

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - Jan 1 2018

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Clinical Trials
Safety
Neoplasms
avelumab
CD274 Antigen
Medical Dictionaries
Therapeutics
National Cancer Institute (U.S.)
Antibodies
Terminology
Fatigue
Immunoglobulin G
Ligands
Drug Therapy

Keywords

  • Avelumab
  • Immunotherapy
  • JAVELIN
  • Programmed death-ligand 1 (PD-L1)
  • Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Kelly, Karen; Infante, Jeffrey R.; Taylor, Matthew H.; Patel, Manish R.; Wong, Deborah J.; Iannotti, Nicholas; Mehnert, Janice M.; Loos, Anja H.; Koch, Helga; Speit, Isabell; Gulley, James L.

In: Cancer, 01.01.2018.

Research output: Contribution to journalArticle

Kelly, Karen ; Infante, Jeffrey R. ; Taylor, Matthew H. ; Patel, Manish R. ; Wong, Deborah J. ; Iannotti, Nicholas ; Mehnert, Janice M. ; Loos, Anja H. ; Koch, Helga ; Speit, Isabell ; Gulley, James L. / 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. In: Cancer. 2018.
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title = "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",
abstract = "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.",
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author = "Karen Kelly and Infante, {Jeffrey R.} and Taylor, {Matthew H.} and Patel, {Manish R.} and Wong, {Deborah J.} and Nicholas Iannotti and Mehnert, {Janice M.} and Loos, {Anja H.} and Helga Koch and Isabell Speit and Gulley, {James L.}",
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T1 - Safety profile of avelumab in patients with advanced solid tumors

T2 - A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

AU - Kelly, Karen

AU - Infante, Jeffrey R.

AU - Taylor, Matthew H.

AU - Patel, Manish R.

AU - Wong, Deborah J.

AU - Iannotti, Nicholas

AU - Mehnert, Janice M.

AU - Loos, Anja H.

AU - Koch, Helga

AU - Speit, Isabell

AU - Gulley, James L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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KW - Programmed death-ligand 1 (PD-L1)

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