First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Branimir I SikicSukhmani K Padda

Abstract

To evaluate the safety, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 (5F9), a humanized IgG4 antibody that targets CD47 to enable phagocytosis. Adult patients with solid tumors were treated in four cohorts: part A, to determine a priming dose; part B, to determine a weekly maintenance dose; part C, to study a loading dose in week 2; and a tumor biopsy cohort. Sixty-two patients were treated: 11 in part A, 14 in B, 22 in C, and 15 in the biopsy cohort. Part A used doses that ranged from 0.1 to 3 mg/kg. On the basis of tolerability and receptor occupancy studies that showed 100% CD47 saturation on RBCs, 1 mg/kg was selected as the priming dose. In subsequent groups, patients were treated with maintenance doses that ranged from 3 to 45 mg/kg, and most toxicities were mild to moderate. These included transient anemia (57% of patients), hemagglutination on peripheral blood smear (36%), fatigue (64%), headaches (50%), fever (45%), chills (45%), hyperbilirubinemia (34%), lymphopenia (34%), infusion-related reactions (34%), and arthralgias (18%). No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximatel...Continue Reading

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Citations

Feb 28, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·André Veillette, Zhenghai Tang
Oct 4, 2019·Nature·Olivier DemariaEric Vivier
Apr 25, 2020·Cancers·Veronica Mendoza-ReinosoPierrick G J Fournier
Jul 1, 2020·Journal of Drug Targeting·Xiaoyu ZhangYanhong Wang
Aug 30, 2019·Nature Reviews. Cancer·Mingye FengIrving L Weissman
Mar 3, 2020·Frontiers in Immunology·Luise MüllerMarc Schmitz
May 14, 2020·International Journal of Molecular Sciences·Anna PastòAntonio Sica
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Jan 13, 2021·Cancers·Marc ArmengolGaël Roué

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