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Xiang H, Liu L, Gao Y, et al. Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials. Cancer Chemother Pharmacol. 2021;88(5):899-910doi: 10.1007/s00280-021-04333-y.
Xiang, H., Liu, L., Gao, Y., Ahene, A., & Collins, H. (2021). Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials. Cancer chemotherapy and pharmacology, 88(5), 899-910. https://doi.org/10.1007/s00280-021-04333-y
Xiang, Hong, et al. "Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials." Cancer chemotherapy and pharmacology vol. 88,5 (2021): 899-910. doi: https://doi.org/10.1007/s00280-021-04333-y
Xiang H, Liu L, Gao Y, Ahene A, Collins H. Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials. Cancer Chemother Pharmacol. 2021 Nov;88(5):899-910. doi: 10.1007/s00280-021-04333-y. Epub 2021 Aug 12. PMID: 34383128; PMCID: PMC8484135.
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Cancer Chemother Pharmacol. 2021 Nov;88(5):899-910. doi: 10.1007/s00280-021-04333-y. Epub 2021 Aug 12.

Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials.

Cancer chemotherapy and pharmacology

Hong Xiang, Lucy Liu, Yuying Gao, Ago Ahene, Helen Collins

Affiliations

  1. Five Prime Therapeutics, Inc., South San Francisco, CA, USA. [email protected].
  2. Amgen Inc., 1120 Veterans Blvd, South San Francisco, CA, 94080, USA. [email protected].
  3. Shanghai Qiangshi Information Technology Co., Ltd., Shanghai, China.
  4. Five Prime Therapeutics, Inc., South San Francisco, CA, USA.
  5. Amgen Inc., 1120 Veterans Blvd, South San Francisco, CA, 94080, USA.

PMID: 34383128 PMCID: PMC8484135 DOI: 10.1007/s00280-021-04333-y

Abstract

PURPOSE: A population pharmacokinetic (PK) analysis of the anti-fibroblast growth factor receptor 2b antibody, bemarituzumab, was performed to evaluate the impact of covariates on the PK and assess whether dose adjustment is necessary for a future phase 3 trial.

METHODS: Serum concentration data were obtained from three clinical trials, with 1552 bemarituzumab serum samples from 173 patients, and were analyzed using nonlinear mixed-effects modeling.

RESULTS: A two-compartment model with parallel linear and nonlinear (Michaelis-Menten) elimination from the central compartment best described the bemarituzumab serum concentration data. The final model estimated a typical linear clearance (CL) of 0.311 L/day, volume of distribution in the central compartment (V

CONCLUSION: No covariate had a clinically meaningful impact on bemarituzumab exposure. These results indicate that dose adjustment of bemarituzumab is not necessary, based on the aforementioned covariates, for a future phase 3 trial in gastric and gastroesophageal junction adenocarcinoma population with FGFR2b overexpression in combination with mFOLFOX6.

© 2021. The Author(s).

Keywords: Anti-fibroblast growth factor receptor 2b; Bemarituzumab; Gastric and gastroesophageal adenocarcinoma; Population pharmacokinetics

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