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      Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial

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          Abstract

          Background

          Avelumab, a fully human IgG1 immune checkpoint inhibitor targeting programmed death ligand 1 (PD-L1), has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours. Here, we assessed avelumab treatment in patients with advanced, platinum-treated non-small cell lung cancer (NSCLC).

          Methods

          In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 sites in the United States. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or nonsquamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary endpoint was safety and tolerability. Secondary endpoints included best overall response, progression-free survival, overall survival, and clinical activity associated with PD-L1 expression. Responses were evaluated using RECIST v1.1, and analyses of antitumour activity and safety were performed in all patients who received at least one dose of avelumab. This trial is registered with ClinicalTrials.gov (NCT01772004); enrolment in this cohort is closed and the trial is ongoing.

          Findings

          Between 10 September 2013 and 24 June 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (interquartile range [first and third quartiles], 7·2–11·9 months). The most common treatment-related adverse events of any grade were fatigue (n=46; 25%), infusion-related reaction (n=38; 21%), and nausea (n=23; 13%). Grade ≥3 treatment-related adverse events occurred in 23 of 184 patients (13%); the most common were infusion-related reaction (n=4; 2%), elevated lipase (n=3; 2%), constipation (n=2; 1%), and dyspnoea (n=2; 1%). 16 of 184 patients (9%) had a serious adverse event related to treatment with avelumab, with infusion-related reaction (4 [2%]) and dyspnoea (2 [1%]) occurring in more than one patient. Immune-related treatment-related events occurred in 22 patients (12%). The confirmed objective response rate, regardless of PD-L1 status, was 12% (95% CI, 8–18), including one complete response and 21 partial responses. Seventy patients had stable disease, for an overall disease-control rate of 50%.

          Interpretation

          Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or resistant NSCLC, providing a rationale for additional studies of avelumab in this disease setting.

          Funding

          Merck KGaA, Darmstadt, Germany and Pfizer, Inc, New York, USA.

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          Author and article information

          Journal
          100957246
          27004
          Lancet Oncol
          Lancet Oncol.
          The Lancet. Oncology
          1470-2045
          1474-5488
          18 May 2017
          31 March 2017
          May 2017
          01 May 2018
          : 18
          : 5
          : 599-610
          Affiliations
          Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, and Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA (James L. Gulley MD); Thoracic and Gastrointestinal Oncology Branch National Cancer Institute, National institutes of Health Bethesda, MD, USA (Arun Rajan MD); Sarah Cannon Research Institute Tennessee Oncology, North Nashville, TN, USA (David R Spigel MD); Hematology Oncology Associates of the Treasure Coast, Port St. Lucie, FL, USA (Nicholas Iannotti MD); West Cancer Center, Memphis, TN, USA (Jason Chandler MD); Department of Medicine, University of California, Los Angeles, CA, USA (Deborah J. L. Wong MD); Virginia Piper Cancer Institute, Minneapolis, MN, USA (Joseph Leach MD); Institute for Translational Oncology Research, Greenville, SC, USA (W. Jeff Edenfield MD); Henry Ford Hospital, Detroit, MI, USA (Ding Wang MD); Merck KGaA, Darmstadt, Germany (Hans Juergen Grote MD, Anja von Heydebreck, PhD); EMD Serono, Inc., Billerica, MA, USA (Kevin Chin MD, Jean-Marie Cuillerot MD); University of California-Davis, Comprehensive Cancer Center, Sacramento, CA, USA (Karen Kelly MD)
          Article
          PMC5522719 PMC5522719 5522719 nihpa866690
          10.1016/S1470-2045(17)30240-1
          5522719
          28373005
          4fb697b8-c4e1-40b9-aac9-caced2114b35
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