First-in-human study of JNJ-63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia
| Autor: | Michael Boyiadzis, Pinkal Desai, Nikki Daskalakis, William Donnellan, Lucille Ferrante, Jenna D. Goldberg, Michael R. Grunwald, Christina Guttke, Xiang Li, Jose Antonio Perez‐Simon, Olga Salamero, Trevor Tucker, Xiaoying Xu, Jay Yang, Naveen Pemmaraju, Juan Manuel Alonso‐Dominguez |
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| Přispěvatelé: | Institut Català de la Salut, [Boyiadzis M] Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. [Desai P] Weill Cornell Medicine, New YorkPresbyterian, New York, New York, USA. [Daskalakis N, Ferrante L] Janssen Research & Development, Spring House, Pennsylvania, USA. [Donnellan W] rah Cannon Research Institute/ Tennessee Oncology, Nashville, Tennessee, USA. [Goldberg JD] Janssen Research & Development, Somerville, New Jersey, USA. [Salamero O] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda::leucemia monocítica aguda [ENFERMEDADES]
Otros calificadores::/uso terapéutico [Otros calificadores] General Neuroscience Medicaments antineoplàstics - Ús terapèutic Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] General Medicine Other subheadings::Other subheadings::/drug therapy [Other subheadings] General Biochemistry Genetics and Molecular Biology Leucèmia mieloide aguda - Tractament Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia Myeloid::Leukemia Myeloid Acute::Leukemia Monocytic Acute [DISEASES] Other subheadings::/therapeutic use [Other subheadings] General Pharmacology Toxicology and Pharmaceutics Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] |
| Zdroj: | Scientia |
| Popis: | Targeting antibody; Acute myeloid leukemia Anticòs dirigit; Leucèmia mieloide aguda Anticuerpo dirigido; Leucemia mieloide aguda This study aimed to identify a recommended phase II dose and evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary clinical activity of JNJ-63709178, a CD123/CD3 dual-targeting antibody, in patients with relapsed or refractory acute myeloid leukemia. Intravenous (i.v.) and subcutaneous (s.c.) administration of JNJ-63709178 were evaluated. The i.v. infusions were administered once every 2 weeks (cohorts 1–5 [n = 17]) or twice weekly (cohorts 6–11 [n = 36]). A twice-weekly s.c. dosing regimen with step-up dosing was also studied (s.c. cohorts 1–2 [n = 9]). Treatment-emergent adverse events (TEAEs) greater than or equal to grade 3 were observed in 11 (65%) patients in cohorts 1–5 and 33 (92%) patients in cohorts 6–11. At the highest i.v. dose (4.8 μg/kg), 5 (71%) patients discontinued treatment due to TEAEs. For s.c. administration (n = 9), eight (89%) patients experienced TEAEs greater than or equal to grade 3 and injection site reactions (≤ grade 3) emerged in all patients. At 4.8 μg/kg (i.v. and s.c.), the mean maximum serum concentrations were 30.3 and 3.59 ng/ml, respectively. Increases in multiple cytokines were observed following i.v. and s.c. administrations, and step-up dosing strategies did not mitigate cytokine production or improve the safety profile and led to limited duration of treatment. Minimal clinical activity was observed across all cohorts. The i.v. and s.c. dosing of JNJ-63709178 was associated with suboptimal drug exposure, unfavorable safety profiles, limited clinical activity, and inability to identify a recommended phase II dose. This work was supported by Janssen Research and Development, LLC. |
| Databáze: | OpenAIRE |
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