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Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia

Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently...

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Autores principales: Ravandi, Farhad, Bashey, Asad, Foran, James, Stock, Wendy, Mawad, Raya, Short, Nicholas, Yilmaz, Musa, Kantarjian, Hagop, Odenike, Olatoyosi, Patel, Anand, Garcha, Raman, Ainsworth, William Barrett, Clynes, Raphael, Kanodia, Jitendra, Ding, Ying, Li, Huajiang, Kye, Steve, Mims, Alice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632668/
https://www.ncbi.nlm.nih.gov/pubmed/37647601
http://dx.doi.org/10.1182/bloodadvances.2023010956
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author Ravandi, Farhad
Bashey, Asad
Foran, James
Stock, Wendy
Mawad, Raya
Short, Nicholas
Yilmaz, Musa
Kantarjian, Hagop
Odenike, Olatoyosi
Patel, Anand
Garcha, Raman
Ainsworth, William Barrett
Clynes, Raphael
Kanodia, Jitendra
Ding, Ying
Li, Huajiang
Kye, Steve
Mims, Alice
author_facet Ravandi, Farhad
Bashey, Asad
Foran, James
Stock, Wendy
Mawad, Raya
Short, Nicholas
Yilmaz, Musa
Kantarjian, Hagop
Odenike, Olatoyosi
Patel, Anand
Garcha, Raman
Ainsworth, William Barrett
Clynes, Raphael
Kanodia, Jitendra
Ding, Ying
Li, Huajiang
Kye, Steve
Mims, Alice
author_sort Ravandi, Farhad
collection PubMed
description Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study’s primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response syndrome (CRS), followed by weekly dosing (1.7 μg/kg, Cohort -1D). In 16 of 120 patients, at least 1 treatment-emergent adverse event was classified as a dose-limiting toxicity. CRS, the most common adverse event (59.2%), managed with premedication, were mostly ≤grade 2. A secondary objective was assessment of efficacy in patients with CD123-expressing leukemias. A total of 10 of 111 (9.0%) efficacy-evaluable patients with AML achieved an overall response of morphologic leukemia-free state or better with an overall objective response rate (ORR) of 9.0%. Response was only observed in patients receiving a target dose of 0.75 μg/kg or higher (n = 87) in which the efficacy-evaluable ORR was 11.5%. Response was associated with lower baseline blast counts in blood and bone marrow (<25%) suggesting potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT02730312.
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spelling pubmed-106326682023-11-10 Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia Ravandi, Farhad Bashey, Asad Foran, James Stock, Wendy Mawad, Raya Short, Nicholas Yilmaz, Musa Kantarjian, Hagop Odenike, Olatoyosi Patel, Anand Garcha, Raman Ainsworth, William Barrett Clynes, Raphael Kanodia, Jitendra Ding, Ying Li, Huajiang Kye, Steve Mims, Alice Blood Adv Clinical Trials and Observations Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study’s primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response syndrome (CRS), followed by weekly dosing (1.7 μg/kg, Cohort -1D). In 16 of 120 patients, at least 1 treatment-emergent adverse event was classified as a dose-limiting toxicity. CRS, the most common adverse event (59.2%), managed with premedication, were mostly ≤grade 2. A secondary objective was assessment of efficacy in patients with CD123-expressing leukemias. A total of 10 of 111 (9.0%) efficacy-evaluable patients with AML achieved an overall response of morphologic leukemia-free state or better with an overall objective response rate (ORR) of 9.0%. Response was only observed in patients receiving a target dose of 0.75 μg/kg or higher (n = 87) in which the efficacy-evaluable ORR was 11.5%. Response was associated with lower baseline blast counts in blood and bone marrow (<25%) suggesting potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT02730312. The American Society of Hematology 2023-09-01 /pmc/articles/PMC10632668/ /pubmed/37647601 http://dx.doi.org/10.1182/bloodadvances.2023010956 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical Trials and Observations
Ravandi, Farhad
Bashey, Asad
Foran, James
Stock, Wendy
Mawad, Raya
Short, Nicholas
Yilmaz, Musa
Kantarjian, Hagop
Odenike, Olatoyosi
Patel, Anand
Garcha, Raman
Ainsworth, William Barrett
Clynes, Raphael
Kanodia, Jitendra
Ding, Ying
Li, Huajiang
Kye, Steve
Mims, Alice
Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
title Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
title_full Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
title_fullStr Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
title_full_unstemmed Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
title_short Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
title_sort phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
topic Clinical Trials and Observations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632668/
https://www.ncbi.nlm.nih.gov/pubmed/37647601
http://dx.doi.org/10.1182/bloodadvances.2023010956
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