Davis KL, Fox E, Merchant MS, Reid JM, Kudgus RA, Liu X, Minard CG, Voss S, Berg SL, Weigel BJ, Mackall CL. Nivolumab in children and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412): a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2020 Apr;21(4):541-550. doi: 10.1016/S1470-2045(20)30023-1. Epub 2020 Mar 17. PMID: 32192573; PMCID: PMC7255545.
Publication Citation
Abstract
Immune checkpoint inhibitors targeting PD-1 have demonstrated clinical benefit in adults with cancer, but experience is limited in children. We conducted a Phase 1/2 study of nivolumab, a PD-1 blocking monoclonal antibody, to determine its safety, pharmacokinetics, and efficacy in children and young adults with recurrent or refractory, non-CNS solid tumors. ADVL1412 is identified as NCT02304458. Analyses were conducted per protocol. Part A enrolled patients 1–18 years with measurable disease regardless of histology and assessed safety and pharmacokinetics of nivolumab (3 mg/kg) administered intravenously every 14 days in 28 day cycles. Part B administered nivolumab intravenously (3 mg/kg) to patients aged 1–30 yrs with measurable disease in the following disease cohorts: rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, neuroblastoma, Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and melanoma. Response was measured by RECIST v1.1. PD-L1 expression and immune cell infiltration was assessed via immunohistochemistry of archival tumor tissue. Primary objectives were to determine the tolerability, systemic exposure, and dosage of nivolumab and the anti-tumor effects at the adult recommended dose chidren and young adults. The trial is ongoing; single-agent nivolumab strata are completed, enrolling between February 22, 2015 – December 31, 2018.