Unknown

Dataset Information

0

Model-Based Population Pharmacokinetic Analysis of Nivolumab in Chinese Patients With Previously Treated Advanced Solid Tumors, Including Non-Small Cell Lung Cancer.


ABSTRACT: Nivolumab is the first anti-programmed death-1 agent approved in China for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Here, we characterize the population pharmacokinetics (PPK) of nivolumab monotherapy in Chinese patients with previously treated advanced/recurrent solid tumors, including NSCLC and nasopharyngeal cancer (NPC), using data from 2 predominantly Chinese (CheckMate 077 and 078), and 5 global (MDX1106-01, CA209-003, and CheckMate 017, 057, and 063) studies. The PPK model was developed by reestimating parameters of a prior global population model with Chinese patient data. Model reestimates showed nivolumab pharmacokinetics (PK) to be linear and dose proportional. Race did not have a clinically meaningful effect on nivolumab clearance. Body weight, Asian race, sex, and performance status had significant effects on clearance. Baseline clearance was 9% lower in the Asian versus the global population but not considered clinically relevant. Change in time-varying clearance and predicted nivolumab exposures with 3 mg/kg every 2 weeks (Q2W) were similar in Chinese, non-Chinese Asian, and non-Asian patients. In Chinese patients, the predicted nivolumab exposure with a 240-mg Q2W regimen was ∼25% higher than with 3 mg/kg Q2W, but ∼62% lower than that of a previously evaluated, well-tolerated regimen of 10 mg/kg Q2W (global population). Differences in nivolumab baseline clearance and exposures between patients with NPC and NSCLC were not clinically meaningful (<20%). Overall, PPK analysis demonstrated that nivolumab was not sensitive to race when evaluated in Chinese and non-Asian patients and exhibited similar PK in NSCLC and NPC.

SUBMITTER: Zhang J 

PROVIDER: S-EPMC6767401 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6656473 | BioStudies
1000-01-01 | S-EPMC5834087 | BioStudies
2020-01-01 | S-EPMC7540331 | BioStudies
1000-01-01 | S-EPMC6263664 | BioStudies
2019-01-01 | S-EPMC6907258 | BioStudies
2016-01-01 | S-EPMC4975160 | BioStudies
2017-01-01 | S-EPMC6075826 | BioStudies
2019-01-01 | S-EPMC7193685 | BioStudies
2020-01-01 | S-EPMC7507990 | BioStudies
2020-01-01 | S-EPMC6989620 | BioStudies