PT - JOURNAL ARTICLE AU - Ulrich Keilholz AU - Janice M. Mehnert AU - Sebastian Bauer AU - Hugues Bourgeois AU - Manish R. Patel AU - Donald Gravenor AU - John J. Nemunaitis AU - Matthew H. Taylor AU - Lucjan Wyrwicz AU - Keun-Wook Lee AU - Vijay Kasturi AU - Kevin Chin AU - Anja von Heydebreck AU - James L. Gulley TI - Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial AID - 10.1186/s40425-018-0459-y DP - 2019 Dec 01 TA - Journal for ImmunoTherapy of Cancer PG - 12 VI - 7 IP - 1 4099 - http://jitc.bmj.com/content/7/1/12.short 4100 - http://jitc.bmj.com/content/7/1/12.full SO - J Immunother Cancer2019 Dec 01; 7 AB - 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)—a human anti–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, 16.1–31.5). 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, 0–4), including ipilimumab (n = 26 [51.0%]). The confirmed ORR was 21.6% (95% CI, 11.3–35.3; 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, 1.4–6.3) 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% [16.9–49.3]), PD-L1–positive tumors (42.1% [20.3–66.5]), or prior ipilimumab therapy (30.8% [14.3–51.8]). 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