PMID- 35262780 OWN - NLM STAT- MEDLINE DCOM- 20220913 LR - 20220919 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 71 IP - 10 DP - 2022 Oct TI - Avelumab in paediatric patients with refractory or relapsed solid tumours: dose-escalation results from an open-label, single-arm, phase 1/2 trial. PG - 2485-2495 LID - 10.1007/s00262-022-03159-8 [doi] AB - BACKGROUND: We report dose-escalation results from an open-label, phase 1/2 trial evaluating avelumab (anti-PD-L1) in paediatric patients with refractory/relapsed solid tumours. METHODS: In phase 1, patients aged < 18 years with solid (including central nervous system [CNS]) tumours for which standard therapy did not exist or had failed were enrolled in sequential cohorts of 3-6 patients. Patients received avelumab 10 or 20 mg/kg intravenously every 2 weeks. Primary endpoints were dose-limiting toxicities (DLTs) and grade >/= 3 treatment-emergent adverse events (AEs). RESULTS: At data cut-off (27 July 2021), 21 patients aged 3-17 years had received avelumab 10 mg/kg (n = 6) or 20 mg/kg (n = 15). One patient had three events that were classified as a DLT (fatigue with hemiparesis and muscular weakness associated with pseudoprogression; 20 mg/kg cohort). Grade >/= 3 AEs occurred in five (83%) and 11 (73%) patients in the 10 and 20 mg/kg cohorts, respectively, and were treatment-related in one patient (7%; grade 3 [DLT]) in the 20 mg/kg cohort. Avelumab exposure in paediatric patients receiving 20 mg/kg dosing, but not 10 mg/kg, was comparable or higher compared with approved adult dosing (10 mg/kg or 800 mg flat dose). No objective responses were observed. Four patients with CNS tumours (20 mg/kg cohort) achieved stable disease, which was ongoing in two patients with astrocytoma at cut-off (for 24.7 and 30.3 months). CONCLUSION: In paediatric patients with refractory/relapsed solid tumours, avelumab monotherapy showed a safety profile consistent with previous adult studies, but clinical benefits were limited. CI - (c) 2022. The Author(s). FAU - Loeb, David M AU - Loeb DM AD - Division of Pediatric Hematology, Oncology, and Cellular Therapy, Children's Hospital at Montefiore, Bronx, NY, USA. FAU - Lee, Ji Won AU - Lee JW AD - Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Morgenstern, Daniel A AU - Morgenstern DA AD - Department of Paediatrics, The Hospital for Sick Children, and University of Toronto, Toronto, ON, Canada. FAU - Samson, Yvan AU - Samson Y AD - Department of Paediatrics, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, QC, Canada. FAU - Uyttebroeck, Anne AU - Uyttebroeck A AD - Department of Pediatric Hematology and Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. FAU - Lyu, Chuhl Joo AU - Lyu CJ AD - Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Van Damme, An AU - Van Damme A AD - Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium. FAU - Nysom, Karsten AU - Nysom K AD - Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark. FAU - Macy, Margaret E AU - Macy ME AD - Department of Pediatrics, University of Colorado Anschutz Medical Campus, and Children's Hospital Colorado, Aurora, CO, USA. FAU - Zorzi, Alexandra P AU - Zorzi AP AD - Children's Hospital, London Health Sciences Centre, London, ON, Canada. FAU - Xiong, Julia AU - Xiong J AD - EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. FAU - Pollert, Petra AU - Pollert P AD - Merck Healthcare KGaA, Darmstadt, Germany. FAU - Joerg, Ingrid AU - Joerg I AD - Merck Healthcare KGaA, Darmstadt, Germany. FAU - Vugmeyster, Yulia AU - Vugmeyster Y AD - EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. FAU - Ruisi, Mary AU - Ruisi M AD - EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. FAU - Kang, Hyoung Jin AU - Kang HJ AUID- ORCID: 0000-0003-1009-6002 AD - Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Wide River Institute of Immunology, Seoul National University Children's Hospital, Seoul, Republic of Korea. kanghj@snu.ac.kr. LA - eng SI - ClinicalTrials.gov/NCT03451825 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article DEP - 20220309 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Antibodies, Monoclonal, Humanized) RN - KXG2PJ551I (avelumab) SB - IM MH - *Antibodies, Monoclonal, Humanized/adverse effects MH - Child MH - Cohort Studies MH - Fatigue MH - Humans MH - *Neoplasms/drug therapy/pathology PMC - PMC9463244 OTO - NOTNLM OT - Avelumab OT - Immune checkpoint inhibitor OT - Immunotherapy OT - Paediatrics OT - Phase 1 COIS- DAM reports serving as a consultant or advisor for Bayer, Boehringer Ingelheim, Clarity Pharmaceuticals, Roche, and Y-mAbs Therapeutics; is a member of a speakers bureau for EUSA Pharma; has received institutional research funding from Bristol Myers Squibb; and has received reimbursement for travel and accommodation expenses from EUSA Pharma and Y-mAbs Therapeutics. KN has received honoraria from and reports serving as a consultant or advisor for Bayer and Y-mAbs Therapeutics. MEM reports serving as a consultant or advisor for Ventana Medical Systems; has received institutional research funding from Bayer, Ignyta, Lilly, MSD, and Roche; holds stock in GE Healthcare, Johnson & Johnson, Teva Pharmaceuticals, and Varian Medical Systems; and has a patent for non-invasive methods of leukaemia cell detection with magnetic resonance imaging/magnetic resonance spectroscopy (US patent 8,894,975). JX was employed by EMD Serono Research & Development Institute Inc., Billerica, MA, USA, an affiliate of Merck KGaA at the time of manuscript preparation. PP and IJ report employment with Merck Healthcare KGaA, Darmstadt, Germany. YV reports employment with EMD Serono Research & Development Institute Inc., Billerica, MA, USA, an affiliate of Merck KGaA. MR reports employment with EMD Serono Research & Development Institute Inc., Billerica, MA, USA, an affiliate of Merck KGaA at the time of manuscript preparation, and holds stock in Bristol Myers Squibb. All other authors declare no competing interests. EDAT- 2022/03/10 06:00 MHDA- 2022/09/14 06:00 PMCR- 2022/03/09 CRDT- 2022/03/09 12:33 PHST- 2021/04/06 00:00 [received] PHST- 2022/01/19 00:00 [accepted] PHST- 2022/03/10 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/03/09 12:33 [entrez] PHST- 2022/03/09 00:00 [pmc-release] AID - 10.1007/s00262-022-03159-8 [pii] AID - 3159 [pii] AID - 10.1007/s00262-022-03159-8 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2022 Oct;71(10):2485-2495. doi: 10.1007/s00262-022-03159-8. Epub 2022 Mar 9.