CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research
ABSTRACT Despite advancements in treatment for B‐cell non‐Hodgkin lymphoma (B‐NHL) in recent decades, many patients still relapse or are refractory to treatment, which represents a high unmet medical need. Novel CD20 × CD3 T‐cell–engaging bispecific antibodies (bsAbs) have created a new paradigm for...
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| Format: | Article |
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Wiley
2025-06-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70250 |
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| author | Min Zhu Xiaowen Guan Samit Ganguly Erik Welf John D. Davis |
| author_facet | Min Zhu Xiaowen Guan Samit Ganguly Erik Welf John D. Davis |
| author_sort | Min Zhu |
| collection | DOAJ |
| description | ABSTRACT Despite advancements in treatment for B‐cell non‐Hodgkin lymphoma (B‐NHL) in recent decades, many patients still relapse or are refractory to treatment, which represents a high unmet medical need. Novel CD20 × CD3 T‐cell–engaging bispecific antibodies (bsAbs) have created a new paradigm for the treatment of B‐NHL. Pivotal studies of four CD20 × CD3 bsAbs, mosunetuzumab, glofitamab, epcoritamab, and odronextamab, as monotherapy, have demonstrated robust responses with generally manageable safety profiles in patients with relapsed or refractory follicular lymphoma and diffuse large B‐cell lymphoma after ≥ 2 lines of systemic therapy. These agents have presented unique challenges (e.g., cytokine release syndrome [CRS]), which have required different strategies to overcome. This review provides a comprehensive overview of the clinical development of these four CD20 × CD3 bsAbs that have been investigated for the treatment of B‐NHL, with a specific focus on translational assessments to select starting doses in first‐in‐human studies, management of CRS, application of modeling and simulation approaches to aid dose escalation and optimization/selection, and strategies used in the design of phase I–III clinical trials. By highlighting learnings and experiences from these four bsAbs assessed, which have not been summarized collectively elsewhere, we aim to promote more efficient study design for novel bsAbs in B‐NHL in the future. |
| format | Article |
| id | doaj-art-8d99b2e94e9b4c45b7a54f688ae106ab |
| institution | Matheson Library |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Clinical and Translational Science |
| spelling | doaj-art-8d99b2e94e9b4c45b7a54f688ae106ab2025-06-26T13:31:16ZengWileyClinical and Translational Science1752-80541752-80622025-06-01186n/an/a10.1111/cts.70250CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical ResearchMin Zhu0Xiaowen Guan1Samit Ganguly2Erik Welf3John D. Davis4Regeneron Pharmaceuticals, Inc. Tarrytown New York USARegeneron Pharmaceuticals, Inc. Tarrytown New York USARegeneron Pharmaceuticals, Inc. Tarrytown New York USARegeneron Pharmaceuticals, Inc. Tarrytown New York USARegeneron Pharmaceuticals, Inc. Tarrytown New York USAABSTRACT Despite advancements in treatment for B‐cell non‐Hodgkin lymphoma (B‐NHL) in recent decades, many patients still relapse or are refractory to treatment, which represents a high unmet medical need. Novel CD20 × CD3 T‐cell–engaging bispecific antibodies (bsAbs) have created a new paradigm for the treatment of B‐NHL. Pivotal studies of four CD20 × CD3 bsAbs, mosunetuzumab, glofitamab, epcoritamab, and odronextamab, as monotherapy, have demonstrated robust responses with generally manageable safety profiles in patients with relapsed or refractory follicular lymphoma and diffuse large B‐cell lymphoma after ≥ 2 lines of systemic therapy. These agents have presented unique challenges (e.g., cytokine release syndrome [CRS]), which have required different strategies to overcome. This review provides a comprehensive overview of the clinical development of these four CD20 × CD3 bsAbs that have been investigated for the treatment of B‐NHL, with a specific focus on translational assessments to select starting doses in first‐in‐human studies, management of CRS, application of modeling and simulation approaches to aid dose escalation and optimization/selection, and strategies used in the design of phase I–III clinical trials. By highlighting learnings and experiences from these four bsAbs assessed, which have not been summarized collectively elsewhere, we aim to promote more efficient study design for novel bsAbs in B‐NHL in the future.https://doi.org/10.1111/cts.70250clinical trialsdosedrug developmentexposure responsehematologymodel‐based drug development |
| spellingShingle | Min Zhu Xiaowen Guan Samit Ganguly Erik Welf John D. Davis CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research Clinical and Translational Science clinical trials dose drug development exposure response hematology model‐based drug development |
| title | CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research |
| title_full | CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research |
| title_fullStr | CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research |
| title_full_unstemmed | CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research |
| title_short | CD20×CD3 Bispecific Antibodies in B‐NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research |
| title_sort | cd20 cd3 bispecific antibodies in b nhl a review of translational science pharmacokinetics pharmacodynamics and dose strategy in clinical research |
| topic | clinical trials dose drug development exposure response hematology model‐based drug development |
| url | https://doi.org/10.1111/cts.70250 |
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