Tremelimumab delivers linear pharmacokinetics in patients with advanced solid tumours

A linear pharmacokinetics characterizes tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 human monoclonal antibody of the immunoglobulin G2 κ isotype, in patients with advanced solid tumours, reveals a study.

In addition, tremelimumab consistently displays opposite trends of time-varying clearance as monotherapy and in combination with durvalumab. Significant covariates include baseline body weight and albumin, but conversion from weight-based dosing at 1 mg/kg to 75 mg shows no impact.

In this study, the authors used the NONMEM methodology to build a pooled-analysis population pharmacokinetics model. They pooled data from five studies, including a total of 956 patients and spanning various tumour types and therapy regimens to develop the model. A pooled dataset from four other studies, with 554 patients, was used for external validation. During model development, the authors explored demographic and relevant clinical covariates.

A two-compartment model showed linear pharmacokinetics for tremelimumab, with time-varying clearance (0.276 L/day at baseline) mainly associated with therapy regimen and with changes in disease status. Tremelimumab clearance over 1 year increased by about 16 percent as monotherapy and by about 17 percent as combination therapy.

Pharmacokinetic behaviour was consistent across patient demographics and cancer subtypes. Those with greater body weight and lower albumin levels at baseline showed significantly higher clearance, but no adjustments in the dosage were required. In adults, a flat dose (75 mg) was expected to provide similar exposure to a weight-based dose (1 mg/kg).