Translation of the efficacy of antibody–drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88
Abstract Three semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, Simeoni, Jumbe, and Hybrid, were used for the efficacy translation of RC88 from preclinical to clinical. RC88 is a mesothelin‐targeting antibody–drug conjugate for malignant solid tumor. In the preclinical study, the rela...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-07-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13526 |
| _version_ | 1797781732313792512 |
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| author | Qiaoning Li Ling Wang Jinfeng Zhang Guorui Zhao Zhihao Liu Xinting Ma Jing Jiang |
| author_facet | Qiaoning Li Ling Wang Jinfeng Zhang Guorui Zhao Zhihao Liu Xinting Ma Jing Jiang |
| author_sort | Qiaoning Li |
| collection | DOAJ |
| description | Abstract Three semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, Simeoni, Jumbe, and Hybrid, were used for the efficacy translation of RC88 from preclinical to clinical. RC88 is a mesothelin‐targeting antibody–drug conjugate for malignant solid tumor. In the preclinical study, the relationship between PKs and PDs was determined using the xenograft mouse model derived from ovarian cancer and lung cancer cell lines. A secondary parameter representing the efficacy index of the drug, termed as tumor static concentration (TSC), was calculated using the three semimechanistic PK/PD models. A mechanism‐based target‐mediated drug disposition model was used to predict the human PKs. TSC from mice and predicted human PK were integrated to predict human efficacy dose. Results showed that 2 cell lines were sensitive to drugs, and the predicted efficacy dose was between 0.82 and 1.96 mg/kg q1w. |
| first_indexed | 2024-03-13T00:01:15Z |
| format | Article |
| id | doaj.art-b55a81aab4a64b09af07de1eb1a7f897 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-03-13T00:01:15Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-b55a81aab4a64b09af07de1eb1a7f8972023-07-13T11:52:35ZengWileyClinical and Translational Science1752-80541752-80622023-07-011671232124210.1111/cts.13526Translation of the efficacy of antibody–drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88Qiaoning Li0Ling Wang1Jinfeng Zhang2Guorui Zhao3Zhihao Liu4Xinting Ma5Jing Jiang6RemeGen, Ltd. Yantai Shandong ChinaRemeGen, Ltd. Yantai Shandong ChinaDepartment of Pharmacology Binzhou Medical University Yantai Shandong ChinaRemeGen, Ltd. Yantai Shandong ChinaRemeGen, Ltd. Yantai Shandong ChinaRemeGen, Ltd. Yantai Shandong ChinaRongchang Industry College Shandong ChinaAbstract Three semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, Simeoni, Jumbe, and Hybrid, were used for the efficacy translation of RC88 from preclinical to clinical. RC88 is a mesothelin‐targeting antibody–drug conjugate for malignant solid tumor. In the preclinical study, the relationship between PKs and PDs was determined using the xenograft mouse model derived from ovarian cancer and lung cancer cell lines. A secondary parameter representing the efficacy index of the drug, termed as tumor static concentration (TSC), was calculated using the three semimechanistic PK/PD models. A mechanism‐based target‐mediated drug disposition model was used to predict the human PKs. TSC from mice and predicted human PK were integrated to predict human efficacy dose. Results showed that 2 cell lines were sensitive to drugs, and the predicted efficacy dose was between 0.82 and 1.96 mg/kg q1w.https://doi.org/10.1111/cts.13526 |
| spellingShingle | Qiaoning Li Ling Wang Jinfeng Zhang Guorui Zhao Zhihao Liu Xinting Ma Jing Jiang Translation of the efficacy of antibody–drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88 Clinical and Translational Science |
| title | Translation of the efficacy of antibody–drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88 |
| title_full | Translation of the efficacy of antibody–drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88 |
| title_fullStr | Translation of the efficacy of antibody–drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88 |
| title_full_unstemmed | Translation of the efficacy of antibody–drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88 |
| title_short | Translation of the efficacy of antibody–drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88 |
| title_sort | translation of the efficacy of antibody drug conjugates from preclinical to clinical using a semimechanistic pk pd model a case study with rc88 |
| url | https://doi.org/10.1111/cts.13526 |
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