التفاصيل البيبلوغرافية
| العنوان: |
Modeling of Proliferating CD4 and CD8 T‐Cell Changes to Tremelimumab Exposure in Patients with Unresectable Hepatocellular Carcinoma. |
| المؤلفون: |
Song, Xuyang, Kelley, Robin Kate, Green, Michelle, Standifer, Nathan, Lim, KyoungSoo, Zhou, Diansong, Dunyak, James, Negro, Alejandra, Kurland, John F., Ren, Song, Khan, Anis A., Gibbs, Megan, Abou‐Alfa, Ghassan K. |
| المصدر: |
Clinical Pharmacology & Therapeutics; Oct2023, Vol. 114 Issue 4, p874-882, 9p |
| مصطلحات موضوعية: |
HEPATOCELLULAR carcinoma, CD8 antigen, CD4 antigen, CELL death, T cells, PROGRAMMED cell death 1 receptors |
| مصطلحات جغرافية: |
HIMALAYA Mountains |
| مستخلص: |
The STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen of single‐dose tremelimumab 300 mg, plus durvalumab 1,500 mg every 4 weeks demonstrated potential for long‐term survival in studies of unresectable hepatocellular carcinoma (uHCC; Study 22 and HIMALAYA). The aim of this analysis was to investigate changes in proliferating CD4+ Ki67+ and CD8+ Ki67+ T cells and their relationship with tremelimumab exposure in patients with uHCC. Median cell count, change from baseline, and percent change from baseline in CD4+ and CD8+ T cells peaked around 14 days after STRIDE. A model of CD4+ and CD8+ T cell response to tremelimumab exposure was developed. Patients with lower baseline T cell counts had a greater percent change from baseline in T cell response to tremelimumab, and baseline T‐cell count was included in the final model. With the full covariate model, the half‐maximal effective concentration (EC50) of tremelimumab was 6.10 μg/mL (standard error = 1.07 μg/mL); > 98.0% of patients were predicted to have a minimum plasma concentration greater than EC50 with tremelimumab 300 or 750 mg. For EC75 (9.82 μg/mL), 69.5% and 98.2% of patients were predicted to exceed the EC75 with tremelimumab 300 and 750 mg, respectively. This analysis supports the clinical hypothesis that combination anti‐cytotoxic T‐lymphocyte‐associated antigen 4 (anti‐CTLA‐4) and anti‐programmed cell death ligand‐1 (anti‐PD‐L1) therapy primes an immune response that may then be sustained by anti‐PD‐L1 monotherapy and supports the clinical utility of the STRIDE regimen in patients with uHCC. These insights may also help inform dose selection of anti‐CTLA‐4 plus anti‐PD‐L1 combination strategies. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
