Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study

Introduction Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avel...

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Main Authors: James L Gulley, Jaafar Bennouna, Guy Jerusalem, Janice Mehnert, Matthew Taylor, Karen Kelly, David Spigel, Marcis Bajars, Claire F Verschraegen, Edward F McClay, Nicholas Iannotti, Charles H Redfern, Franklin L Chen, John C Morris, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi
Format: Article
Language:English
Published: BMJ Publishing Group 2020-10-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/8/2/e001064.full
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author James L Gulley
Jaafar Bennouna
Guy Jerusalem
Janice Mehnert
Matthew Taylor
Karen Kelly
David Spigel
Marcis Bajars
Claire F Verschraegen
Edward F McClay
Nicholas Iannotti
Charles H Redfern
Franklin L Chen
John C Morris
Ding Wang
Hans Juergen Grote
Dongli Zhou
Neru Munshi
author_facet James L Gulley
Jaafar Bennouna
Guy Jerusalem
Janice Mehnert
Matthew Taylor
Karen Kelly
David Spigel
Marcis Bajars
Claire F Verschraegen
Edward F McClay
Nicholas Iannotti
Charles H Redfern
Franklin L Chen
John C Morris
Ding Wang
Hans Juergen Grote
Dongli Zhou
Neru Munshi
author_sort James L Gulley
collection DOAJ
description Introduction Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).Methods In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.Results Overall, 156 patients were enrolled and treated. Median duration of follow-up was 18.6 months (range, 15 to 23 months). The objective response rate was 19.9% (95% CI, 13.9 to 27.0), including complete response in 3 (1.9%) and partial response in 28 (17.9%). Median DOR was 12.0 months (95% CI, 6.9 to not estimable). Median PFS was 4.0 months (95% CI, 2.7 to 5.4) and the 6-month PFS rate was 38.5% (95% CI, 30.7 to 46.3). Median OS was 14.1 months (95% CI, 11.3 to 16.9) and the 12-month OS rate was 56.6% (95% CI, 48.2 to 64.1). Treatment-related adverse events (TRAEs) occurred in 107 patients (68.6%), including grade ≥3 TRAEs in 19 (12.2%). Immune-related adverse events and infusion-related reactions occurred in 31 (19.9%) and 40 patients (25.6%), respectively. No treatment-related deaths occurred.Conclusion Avelumab showed antitumor activity with a tolerable safety profile as a first-line treatment in patients with advanced NSCLC. These data support further investigation of avelumab in the phase III JAVELIN Lung 100 study.Trial registration details ClinicalTrials.gov NCT01772004; registered January 21, 2013.
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spelling doaj-art-e6b6f8200ed4438aa9844cca535c63842024-11-10T17:15:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001064Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor studyJames L Gulley0Jaafar Bennouna1Guy Jerusalem2Janice Mehnert3Matthew Taylor4Karen Kelly5David Spigel6Marcis Bajars7Claire F Verschraegen8Edward F McClay9Nicholas Iannotti10Charles H Redfern11Franklin L Chen12John C Morris13Ding Wang14Hans Juergen Grote15Dongli Zhou16Neru Munshi177 Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA6 Department of Pneumology, Thoracic Oncology, University Hospital Centre Nantes, Nantes, France2 Department of Medical Oncology, CHU Sart Tilman Liege and Liege University, Liege, Belgium6Perlmutter Cancer Center at NYU Langone, New York, NY, USA11 Providence Cancer Center, Portland, Oregon, USADivison of Hematology and Oncology, Department of Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, California, USAchief scientific officerMerck Healthcare KGaA, Darmstadt, Germany1 Division of Medical Oncology, The Ohio State University James Cancer Hospital, Columbus, Ohio, USA3 Institute for Melanoma Research & Education, California Cancer Associates for Research & Excellence, Encinitas, California, USA4 Hematology Oncology Associates of the Treasure Coast, Port St. Lucie, Florida, USA5 Sharp Healthcare, San Diego, California, USA7 Novant Health Oncology Specialists, Winston-Salem, North Carolina, USADepartment of Neurology, Washington University School of Medicine, St. Louis, Missouri, USAHenry Ford Health System, Detroit, Michigan, USAMerck Healthcare KGaA, Darmstadt, GermanyMerck Serono (Beijing) Pharmaceutical R&D Co., Ltd., Beijing, China, an affiliate of Merck KGaA, Beijing, China16 EMD Serono Research & Development Institute, Inc, Billerica, Massachusetts, USA; a business of Merck KGaA, Darmstadt, GermanyIntroduction Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).Methods In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.Results Overall, 156 patients were enrolled and treated. Median duration of follow-up was 18.6 months (range, 15 to 23 months). The objective response rate was 19.9% (95% CI, 13.9 to 27.0), including complete response in 3 (1.9%) and partial response in 28 (17.9%). Median DOR was 12.0 months (95% CI, 6.9 to not estimable). Median PFS was 4.0 months (95% CI, 2.7 to 5.4) and the 6-month PFS rate was 38.5% (95% CI, 30.7 to 46.3). Median OS was 14.1 months (95% CI, 11.3 to 16.9) and the 12-month OS rate was 56.6% (95% CI, 48.2 to 64.1). Treatment-related adverse events (TRAEs) occurred in 107 patients (68.6%), including grade ≥3 TRAEs in 19 (12.2%). Immune-related adverse events and infusion-related reactions occurred in 31 (19.9%) and 40 patients (25.6%), respectively. No treatment-related deaths occurred.Conclusion Avelumab showed antitumor activity with a tolerable safety profile as a first-line treatment in patients with advanced NSCLC. These data support further investigation of avelumab in the phase III JAVELIN Lung 100 study.Trial registration details ClinicalTrials.gov NCT01772004; registered January 21, 2013.https://jitc.bmj.com/content/8/2/e001064.full
spellingShingle James L Gulley
Jaafar Bennouna
Guy Jerusalem
Janice Mehnert
Matthew Taylor
Karen Kelly
David Spigel
Marcis Bajars
Claire F Verschraegen
Edward F McClay
Nicholas Iannotti
Charles H Redfern
Franklin L Chen
John C Morris
Ding Wang
Hans Juergen Grote
Dongli Zhou
Neru Munshi
Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study
Journal for ImmunoTherapy of Cancer
title Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study
title_full Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study
title_fullStr Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study
title_full_unstemmed Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study
title_short Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study
title_sort efficacy and safety of first line avelumab in patients with advanced non small cell lung cancer results from a phase ib cohort of the javelin solid tumor study
url https://jitc.bmj.com/content/8/2/e001064.full
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