Pharmacokinetics of Odronextamab, A Bispecific T-Cell-Engaging Antibody, in Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma.

Non-Hodgkin lymphoma (NHL) is the fifth most common malignancy and accounts for 5% of all cancers in the US, with the largest proportion being B-cell CD20 positive NHL. Odronextamab is a CD20xCD3 IgG4 bispecific T-cell-engaging monoclonal antibody under development for the treatment of relapsed or refractory (R/R) B-NHL. The objectives of this analysis were to characterize the pharmacokinetics (PK) of odronextamab in adult patients, and elucidate sources and correlates of variability. PK data of 507 patients with R/R B-NHL from ELM-1 (NCT02290951, Phase I; n = 167) and ELM-2 (NCT03888105, Phase II; n = 340) were analyzed. Odronextamab concentration-time profiles following intravenous administration of 0.03 mg to 320 mg doses were described by a bi-exponential decline with parallel linear (first-order) and non-linear (Michaelis-Menten) elimination processes. The modified Michaelis-Menten or target-mediated elimination was not only concentration-dependent but also time-dependent. A reduction in target-mediated clearance over time suggests a reduction in target abundance to a larger extent than associated with concentration alone, which is consistent with the treatment-induced depletion of the B cells observed in patients who underwent assessment. Linear clearance (CL) and steady-state volume of distribution were 0.189 L/day and 9.41 L, respectively. Target-mediated clearance was ~5 L/day at baseline, with an asymptote of ~0.03 L/day at steady state. With the largest covariate effect on odronextamab exposure, baseline body weight was directly correlated with CL and volume of distribution, albumin was inversely correlated with CL and volume of distribution, and baseline interleukin-10 was inversely correlated with CL.