A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies

Abstract

This phase 1 study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of obinutuzumab (GA101), a glycoengineered type II anti-CD20 monoclonal antibody administered as induction followed by 2 years of maintenance.

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics

“…[54][55][56] The nonlinear PK of these types of antibodies may in part be explained by binding of the antibodies to their respective targets, with a large component of target-mediated elimination after the first dose that is chemotherapy) have an elimination half-life in the magnitude of hours and rapidly achieve steady-state following administration (hours-days), while large molecules (e.g., mAbs) have a very long elimination half-life (in the magnitude of weeks) and may take up to 12 weeks to achieve steady-state. 65,66,69,70 …”

“…We also know that the exposure to antibodies depends on a variety of factors, including dose and frequency of administration, distribution, specific and non-specific clearance, amount of tumor. 55 An exact quantification of the effect of each factor, which obviously varies from subject to subject, is, however, difficult to define.…”

Glycoengineering of Therapeutic Antibodies Enhances Monocyte/Macrophage-Mediated Phagocytosis and Cytotoxicity

“…In line with these properties, a number of preclinical studies demonstrated that Ab Fcafucosylation translates into significantly enhanced activity in vivo (6,9,17), and this has led to the approval of new therapeutic GE Abs. GA101 (obinutuzumab) is a GE, type II anti-CD20 mAb that has recently been approved by the U.S. Food and Drug Administration for the first line treatment of patients with chronic lymphocytic leukemia (CLL) in combination with chlorambucil (18)(19)(20). In Japan, the GE CCR4 Ab mogamulizumab has been approved for treatment of patients with relapsed or refractory CCR4 + T cell leukemia-lymphoma (21).…”

Cytokine release in patients with CLL treated with obinutuzumab and possible relationship with infusion-related reactions

“…We analyzed IRR frequency and severity in a subset of 38 patients, the entire complement with an underlying diagnosis of CLL pooled from 2 phase-1/2 trials, GAUSS (#NCT00576758), 10 and GAUGUIN (#NCT00517530). 11 Study methods were as previously published.…”

“…11 Study methods were as previously published. 10,11 Patients were universally treated with obinutuzumab monotherapy and had frequent sequential blood samples taken. This enabled us to interrogate the association of IRR with patient baseline and tumor characteristics, peripheral blood leukocyte subsets, serum cytokine release, and complement activation.…”