Abstract 2044: Pharmacokinetics (PK) of nivolumab in patients with relapsed or refractory lymphoid malignancies
Authors: Wang Xiaoli , Hruska Matthew , Bradley-Garelik M. Brigid , Boone Bradly , Bello Akintunde 
Published: July 2016

Objectives: Nivolumab, a fully human anti-programmed death-1 immunoglobulin G4 antibody, has demonstrated clinically meaningful responses and overall survival benefits in patients with solid tumors following administration of 3 mg/kg every 2 weeks (Q2W)—the currently approved dosing regimen for the treatment of advanced melanoma and non-small-cell lung cancer (NSCLC). Nivolumab has also demonstrated strong antitumor activity in lymphoid malignancies with an objective response rate of 87% in relapsed or refractory classical Hodgkin lymphoma (cHL) (Ansell SM, et al. N Engl J Med. 2015). The present analysis aimed to characterize the PK of nivolumab in 4 different lymphoid malignancies, including multiple myeloma (MM), T-cell non-Hodgkin lymphoma (NHL), B-cell NHL, and cHL, and to compare the PK to that seen in solid tumors.

Methods: This analysis was conducted as part of an open-label, dose-escalation phase 1 study (NCT01592370) investigating the safety, PK, and antitumor activity of nivolumab in patients with relapsed or refractory lymphoid malignancies. Patients were treated with nivolumab 1 mg/kg Q2W or 3 mg/kg Q2W in the dose-escalation phase, and with nivolumab 3 mg/kg Q2W during the dose-expansion phase. Serial blood samples were collected and analyzed for PK using a validated ligand-binding enzyme-linked immunosorbent assay. PK parameters of nivolumab, including area under the curve over the 2-week (336 hours) interval following the first dose (AUC336) and maximum plasma concentration (Cmax) after the first dose were characterized using noncompartmental analysis.

Results: The geometric mean (coefficient of variation [CV]) values of dose-normalized AUC336 of nivolumab in the MM (n = 22), B-cell NHL (n = 30), T-cell NHL (n = 19), and HL (n = 18) groups were 3759 μg•h/mL (23%), 3298 μg•h/mL (24%), 2800 μg•h/mL (29%), and 2977 μg•h/mL (27%), respectively. The geometric mean (CV) values of dose-normalized Cmax of nivolumab in the MM, B-cell NHL, T-cell NHL, and HL groups were 24 μg/mL (30%), 20 μg/mL (26%), 18 μg/mL (31%), and 18 μg/mL (25%), respectively. Dose-normalized exposures were similar at the 1- and 3-mg/kg dose levels.

Conclusions: The PK of nivolumab is similar among patients with different lymphoid malignancies and is similar to what has previously been observed for patients with solid tumors, including melanoma, renal cell carcinoma, and NSCLC, following administration of nivolumab 3 mg/kg Q2W. Based on the observed tolerable safety profile and strong antitumor activity, nivolumab 3 mg/kg Q2W is an appropriate dosing regimen for study in patients with lymphoid malignancies.

Citation Format: Xiaoli Wang, Matthew Hruska, M. Brigid Bradley-Garelik, Bradly Boone, Akintunde Bello. Pharmacokinetics (PK) of nivolumab in patients with relapsed or refractory lymphoid malignancies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2044.