Avelumab in paediatric patients with refractory or relapsed solid tumours: dose-escalation results from an open-label, single-arm, phase 1/2 trial
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Published:2022-03-09
Issue:10
Volume:71
Page:2485-2495
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ISSN:0340-7004
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Container-title:Cancer Immunology, Immunotherapy
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language:en
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Short-container-title:Cancer Immunol Immunother
Author:
Loeb David M., Lee Ji Won, Morgenstern Daniel A., Samson Yvan, Uyttebroeck Anne, Lyu Chuhl Joo, Van Damme An, Nysom Karsten, Macy Margaret E., Zorzi Alexandra P., Xiong Julia, Pollert Petra, Joerg Ingrid, Vugmeyster Yulia, Ruisi Mary, Kang Hyoung JinORCID
Abstract
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Immunology,Immunology and Allergy
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