First‐in‐human study of JNJ‐63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia
Abstract 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. Intraven...
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13467 |
| _version_ | 1797870506944233472 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Michael Boyiadzis |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T00:28:29Z |
| format | Article |
| id | doaj.art-2ed30f1b9d9b4b9aad49fe1caf9fdf6d |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-04-10T00:28:29Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-2ed30f1b9d9b4b9aad49fe1caf9fdf6d2023-03-15T04:35:39ZengWileyClinical and Translational Science1752-80541752-80622023-03-0116342943510.1111/cts.13467First‐in‐human study of JNJ‐63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemiaMichael Boyiadzis0Pinkal Desai1Nikki Daskalakis2William Donnellan3Lucille Ferrante4Jenna D. Goldberg5Michael R. Grunwald6Christina Guttke7Xiang Li8Jose Antonio Perez‐Simon9Olga Salamero10Trevor Tucker11Xiaoying Xu12Jay Yang13Naveen Pemmaraju14Juan Manuel Alonso‐Dominguez15Hillman Cancer Center University of Pittsburgh Medical Center Pittsburgh Pennsylvania USAWeill Cornell Medicine New York‐Presbyterian New York New York USAJanssen Research & Development Spring House Pennsylvania USASarah Cannon Research Institute/Tennessee Oncology Nashville Tennessee USAJanssen Research & Development Spring House Pennsylvania USAJanssen Research & Development Somerville New Jersey USALevine Cancer Institute Atrium Health Charlotte North Carolina USAJanssen Research & Development Spring House Pennsylvania USAJanssen Research & Development Somerville New Jersey USAInstituto de Biomedicina de Sevilla (IBIS/CISC) Universitario Virgen del Rocio, Universidad de Sevilla Sevilla SpainVall d'Hebron University Hospital, VHIO Barcelona SpainJanssen Research & Development Spring House Pennsylvania USAJanssen Research & Development Somerville New Jersey USABarbara Ann Karmanos Cancer Institute Detroit Michigan USAMD Anderson Cancer Center University of Texas Houston Texas USAHematology Department, Early Phase Clinical Trials Unit START Madrid‐FJD Fundacion Jiménez Díaz University Hospital Madrid SpainAbstract 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.https://doi.org/10.1111/cts.13467 |
| spellingShingle | 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 First‐in‐human study of JNJ‐63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia Clinical and Translational Science |
| title | First‐in‐human study of JNJ‐63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia |
| title_full | First‐in‐human study of JNJ‐63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia |
| title_fullStr | First‐in‐human study of JNJ‐63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia |
| title_full_unstemmed | First‐in‐human study of JNJ‐63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia |
| title_short | First‐in‐human study of JNJ‐63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia |
| title_sort | first in human study of jnj 63709178 a cd123 cd3 targeting antibody in relapsed refractory acute myeloid leukemia |
| url | https://doi.org/10.1111/cts.13467 |
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