@article {Keilholz12, author = {Ulrich Keilholz and Janice M. Mehnert and Sebastian Bauer and Hugues Bourgeois and Manish R. Patel and Donald Gravenor and John J. Nemunaitis and Matthew H. Taylor and Lucjan Wyrwicz and Keun-Wook Lee and Vijay Kasturi and Kevin Chin and Anja von Heydebreck and James L. Gulley}, title = {Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial}, volume = {7}, number = {1}, elocation-id = {12}, year = {2019}, doi = {10.1186/s40425-018-0459-y}, publisher = {BMJ Specialist Journals}, abstract = {Background We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after >=1 line of therapy for metastatic disease.Patients and methods Patients received avelumab (10 mg/kg){\textemdash}a human anti{\textendash}PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.Results As of December 31, 2016, 51 patients were treated and followed for a median of 24.2 months (range, 16.1{\textendash}31.5). Most patients had cutaneous (n~= 28 [54.9\%]) or ocular (n~= 16 [31.4\%]) melanoma and had received a median of 2 prior lines of therapy (range, 0{\textendash}4), including ipilimumab (n~= 26 [51.0\%]). The confirmed ORR was 21.6\% (95\% CI, 11.3{\textendash}35.3; complete response, 7.8\%; partial response, 13.7\%). The median duration of response was not estimable (95\% CI, 2.6 months-not estimable). Median PFS and OS were 3.1 months (95\% CI, 1.4{\textendash}6.3) and 17.2 months (95\% CI, 6.6-not estimable), respectively. Subgroup analyses suggested meaningful clinical activity (ORR [95\% CI]) in patients with non-ocular melanoma (31.4\% [16.9{\textendash}49.3]), PD-L1{\textendash}positive tumors (42.1\% [20.3{\textendash}66.5]), or prior ipilimumab therapy (30.8\% [14.3{\textendash}51.8]). Thirty-nine patients (76.5\%) had a treatment-related adverse event (TRAE), most commonly infusion-related reaction (29.4\%), fatigue (17.6\%), and chills (11.8\%); 4 patients (7.8\%) had a grade 3 TRAE. Five patients (9.8\%) had an immune-related TRAE (all were grade 1/2). No grade 4 TRAEs or treatment-related deaths were reported.Conclusion Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in patients with previously treated metastatic melanoma.Trial registration ClinicalTrials.gov identifier: NCT01772004.Abbreviations:AEAdverse eventAJCCAmerican Joint Committee on CancerCIConfidence intervalCTLA-4Cytotoxic T-lymphocyte associated-protein 4DORDuration of responseECOG PSEastern Cooperative Oncology Group performance statusFDAFood and Drug AdministrationHRHazard ratioICIImmune checkpoint inhibitorIgG1Immunoglobulin G1irAEImmune-related AEIRRInfusion-related reactionNCI-CTCAENational Cancer Institute Common Terminology Criteria for Adverse EventsNENot estimableORRObjective response rateOSOverall survivalPD-1Programmed cell death-1PD-L1Programmed death-ligand 1PFSProgression-free survivalQ2Wevery 2 weeksRECISTResponse Evaluation Criteria in Solid TumorsTRAETreatment-related adverse eventUICCUnion for International Cancer Control}, URL = {https://jitc.bmj.com/content/7/1/12}, eprint = {https://jitc.bmj.com/content/7/1/12.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }