TY - JOUR
T1 - First-in-human study of JNJ-63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia
AU - Boyiadzis, Michael
AU - Desai, Pinkal
AU - Daskalakis, Nikki
AU - Donnellan, William
AU - Ferrante, Lucille
AU - Goldberg, Jenna D.
AU - Grunwald, Michael R.
AU - Guttke, Christina
AU - Li, Xiang
AU - Perez-Simon, Jose Antonio
AU - Salamero, Olga
AU - Tucker, Trevor
AU - Xu, Xiaoying
AU - Yang, Jay
AU - Pemmaraju, Naveen
AU - Alonso-Dominguez, Juan Manuel
N1 - Funding Information:
This work was supported by Janssen Research and Development, LLC.
Publisher Copyright:
© 2022 Janssen Research and Development, LLC and The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
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U2 - 10.1111/cts.13467
DO - 10.1111/cts.13467
M3 - Article
C2 - 36564917
AN - SCOPUS:85146357095
SN - 1752-8054
VL - 16
SP - 429
EP - 435
JO - Clinical and translational science
JF - Clinical and translational science
IS - 3
ER -