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.