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Volume 84, Issue 6_Supplement
15 March 2024
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Abstract
Poster Presentations - Proffered Abstracts| March 22 2024
Miranda M.C. van der Lee;
Miranda M.C. van der Lee
1Byondis B.V., Nijmegen, Netherlands;
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Tanja van Achterberg;
Tanja van Achterberg
1Byondis B.V., Nijmegen, Netherlands;
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Kaylee Hersmus;
Kaylee Hersmus
1Byondis B.V., Nijmegen, Netherlands;
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Annet Brouwers-Vos;
Annet Brouwers-Vos
2University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
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Monique van der Vleuten;
Monique van der Vleuten
1Byondis B.V., Nijmegen, Netherlands;
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Maurien Pruis;
Maurien Pruis
2University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
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Wendy Kappers;
Wendy Kappers
1Byondis B.V., Nijmegen, Netherlands;
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Gijs Verheijden;
Gijs Verheijden
1Byondis B.V., Nijmegen, Netherlands;
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Gerwin Huls;
Gerwin Huls
2University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
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Glenn van Wigcheren;
Glenn van Wigcheren
1Byondis B.V., Nijmegen, Netherlands;
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Ruud Ubink;
Ruud Ubink
1Byondis B.V., Nijmegen, Netherlands;
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Aloys Sesink;
Aloys Sesink
1Byondis B.V., Nijmegen, Netherlands;
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Alyson MacInnes;
Alyson MacInnes
1Byondis B.V., Nijmegen, Netherlands;
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Jan Jacob Schuringa;
Jan Jacob Schuringa
2University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
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Wim Dokter
Wim Dokter
1Byondis B.V., Nijmegen, Netherlands;
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Author & Article Information
Online ISSN: 1538-7445
Print ISSN: 0008-5472
©2024 American Association for Cancer Research
2024
American Association for Cancer Research
Cancer Res (2024) 84 (6_Supplement): 3129.
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- Version of Record March 22 2024
Citation
Miranda M.C. van der Lee, Tanja van Achterberg, Kaylee Hersmus, Annet Brouwers-Vos, Monique van der Vleuten, Maurien Pruis, Wendy Kappers, Gijs Verheijden, Gerwin Huls, Glenn van Wigcheren, Ruud Ubink, Aloys Sesink, Alyson MacInnes, Jan Jacob Schuringa, Wim Dokter; Abstract 3129: BYON4413, an in vivo active CD123-targeting antibody-drug conjugate, combines effectively with azacitidine and venetoclax in acute myeloid leukemia cell lines. Cancer Res 15 March 2024; 84 (6_Supplement): 3129. https://doi.org/10.1158/1538-7445.AM2024-3129
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Abstract
Background: CD123, the alpha chain of the interleukin-3 receptor (IL-3Rα), is overexpressed in multiple hematologic malignancies and found particularly highly expressed on the surface of acute myeloid leukemia (AML) cells. Furthermore, increased CD123 expression on leukemic stem cells relative to non-neoplastic hematopoietic stem cells makes CD123 an attractive tumor-associated target for an antibody-drug conjugate (ADC). BYON4413 is an ADC that consists of a novel humanized IgG1 anti-CD123 antibody site-specifically conjugated with Byondis' proprietary duocarmazine linker-drug technology, ByonZine® and ByonShieLD®. The efficacy of BYON4413 is studied as monotherapy and in combination with azacitidine and venetoclax (AZA/VEN), since the AZA/VEN regimen is the standard of care (SOC) for AML patients who are ineligible for intensive chemotherapy.
Method: A panel of CD123+ and CD123- hematological cell lines and AML patient-derived bone marrow mononuclear cells (BMMCs)/peripheral blood mononuclear cells (PBMCs) were utilized in in vitro studies to determine the cytotoxic effects of BYON4413. The induction of apoptosis and cell killing by BYON4413 in a triple combination with AZA/VEN was studied in vitro using the CD123+ AML cell lines MOLM-13 and MV4-11. AML patient and cell line-derived xenograft models were used to investigate the in vivo efficacy of BYON4413.
Results: In vitro studies with human AML cell lines show that BYON4413 is highly effective in eradicating CD123+ cells while having little impact on CD123- cells. These results were confirmed ex vivo with AML patient-derived BMMCs/PBMCs. BYON4413 effectively killed AML patient-derived blasts while largely sparing healthy hematopoietic cells. The triple combination of BYON4413 with AZA/VEN enhanced both apoptosis and cell killing of AML cell lines compared to the singular BYON4413 treatment. In vivo studies demonstrate that BYON4413 is remarkably efficient at reducing the tumor burden in AML patient- and cell line-derived xenograft models.
Conclusions: Preclinical studies show that BYON4413 has potential to be an effective targeted therapy against CD123+ hematological malignancies such as AML. The enhanced efficacy of BYON4413 together with AZA/VEN suggests that a clinical benefit from the triple combination may be achievable and is worth further exploration. A first-in-human dose-escalation and expansion trial with BYON4413, designed to enroll R/R AML and high-risk MDS patients, is scheduled to start in Q2 2024.
Citation Format: Miranda M.C. van der Lee, Tanja van Achterberg, Kaylee Hersmus, Annet Brouwers-Vos, Monique van der Vleuten, Maurien Pruis, Wendy Kappers, Gijs Verheijden, Gerwin Huls, Glenn van Wigcheren, Ruud Ubink, Aloys Sesink, Alyson MacInnes, Jan Jacob Schuringa, Wim Dokter. BYON4413, an in vivo active CD123-targeting antibody-drug conjugate, combines effectively with azacitidine and venetoclax in acute myeloid leukemia cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3129.
©2024 American Association for Cancer Research
2024
American Association for Cancer Research
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