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Avelumab in paediatric patients with refractory or relapsed solid tumours: dose-escalation results from an open-label, single-arm, phase 1/2 trial

 David M Loeb  ;  Ji Won Lee  ;  Daniel A Morgenstern  ;  Yvan Samson  ;  Anne Uyttebroeck  ;  Chuhl Joo Lyu  ;  An Van Damme  ;  Karsten Nysom  ;  Margaret E Macy  ;  Alexandra P Zorzi  ;  Julia Xiong  ;  Petra Pollert  ;  Ingrid Joerg  ;  Yulia Vugmeyster  ;  Mary Ruisi  ;  Hyoung Jin Kang 
 CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol.71(10) : 2485-2495, 2022-10 
Journal Title
Issue Date
Antibodies, Monoclonal, Humanized* / adverse effects ; Child ; Cohort Studies ; Fatigue ; Humans ; Neoplasms* / drug therapy ; Neoplasms* / pathology
Avelumab ; Immune checkpoint inhibitor ; Immunotherapy ; Paediatrics ; Phase 1
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.

Trial registration: ClinicalTrials.gov NCT03451825.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Lyu, Chuhl Joo(유철주) ORCID logo https://orcid.org/0000-0001-7124-7818
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