@article {Le Tourneau111, author = {Christophe Le Tourneau and Christopher Hoimes and Corrine Zarwan and Deborah J. Wong and Sebastian Bauer and Rainer Claus and Martin Wermke and Subramanian Hariharan and Anja von Heydebreck and Vijay Kasturi and Vikram Chand and James L. Gulley}, title = {Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial}, volume = {6}, number = {1}, elocation-id = {111}, year = {2018}, doi = {10.1186/s40425-018-0424-9}, publisher = {BMJ Specialist Journals}, abstract = {Background We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC).Methods In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10~mg/kg intravenously every 2~weeks. Continuation of mitotane was permitted; however, mitotane levels during the study were not recorded. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors v1.1.Results Fifty patients received avelumab and were followed for a median of 16.5~months. Prior treatment included >=2 lines in 74.0\%; mitotane was continued in 50.0\%. The objective response rate (ORR) was 6.0\% (95\% CI, 1.3\% to 16.5\%; partial response in 3 patients). Twenty-one patients (42.0\%) had stable disease as best response (disease control rate, 48.0\%). Median progression-free survival was 2.6~months (95\% CI, 1.4 to 4.0), median overall survival (OS) was 10.6~months (95\% CI, 7.4 to 15.0), and the 1-year OS rate was 43.4\% (95\% CI, 27.9\% to 57.9\%). In evaluable patients with PD-L1+ (n = 12) or PD-L1- (n = 30) tumors (>=5\% tumor cell cutoff), ORR was 16.7\% vs 3.3\% (P = .192). Treatment-related adverse events (TRAEs) occurred in 82.0\%; the most common were nausea (20.0\%), fatigue (18.0\%), hypothyroidism (14.0\%), and pyrexia (14.0\%). Grade 3 TRAEs occurred in 16.0\%; no grade 4 to 5 TRAEs occurred. Twelve patients (24.0\%) had an immune-related TRAE of any grade, which were grade 3 in 2 patients (4.0\%): adrenal insufficiency (n = 1), and pneumonitis (n = 1).Conclusions Avelumab showed clinical activity and a manageable safety profile in patients with platinum-treated mACC.Trial registration Clinicaltrials.gov NCT01772004; registered January 21, 2013.Christophe Le Tourneau and Christopher Hoimes contributed equally to this work.Abbreviations:ACCAdrenocortical carcinomaAEAdverse eventALTAlanine aminotransferaseASTAsparate aminotransferaseCCNE1Cyclin E1CIConfidence intervalCNSCentral nervous systemCRComplete responseECOG PSEastern Cooperative Oncology Group performance statusGGTγ-glutamyltransferaseHRHazard ratiosmACCMetastatic adrenocortical carcinomamTORMammalian Target of RapamycinNENot evaluableNF1Neurofibromin 1ORRObjective response rateOSOverall survivalPD-1Programmed death 1PD-L1Programmed death ligand 1PFSProgression-free survivalPRKAR1AProtein kinase cAMP-dependent type 1 regulatory subunit alphaRECISTResponse Evaluation Criteria In Solid TumorsRPL22Ribosomal protein L22SAESerious adverse eventTERF2Telomeric repeat binding factor 2TERTTelomerase reverse transcriptaseTKITyrosine-kinase inhibitorTRAETreatment-related adverse eventVEGFVascular endothelial growth factorZNRF3Zinc and ring finger 3}, URL = {https://jitc.bmj.com/content/6/1/111}, eprint = {https://jitc.bmj.com/content/6/1/111.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }