Obinutuzumab

Obinutuzumab (GA101) a novel glycoengineered Type II CD20 monoclonal antibody in development for non-Hodgkin lymphoma.

Obinutuzumab is found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it is 10 to 1,000 times less potent in mediating CDC. Obinutuzumab shows superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and is comparable with these two in ADCP. Obinutuzumab also shows slower internalization rate upon binding to CD20 than rituximab and ofatumumab[1]

Obinutuzumab is more active than rituximab administered at similar doses on established RL tumors. The antitumor effect of obinutuzumab against RL xenografts is dose dependent in terms of tumor growth inhibition (TGI). TGI is calculated using NCI formula at day 34 and shows values of 25, 75, and 85% for the 10, 30, and 100 mg/kg dosages of obinutuzumab, respectively. The higher doses of 30 and 100 mg/kg of obinutuzumab significantly inhibit the growth of RL tumors and result in some complete tumor remissions (10% and 30%, respectively). Tolerability of obinutuzumab with these regimens is excellent and no significant modification of body weight is observed[2]. Obinutuzumab induces a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab[1]. Obinutuzumab plus bendamustine achieves superior tumor growth inhibition versus rituximab plus bendamustine and shows a statistically significant effect versus the respective single treatments. Obinutuzumab plus chemotherapy is superior to the respective monotherapies[3].

[1]. Herter S, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013 Oct;12(10):2031-42. [2]. Dalle S, et al. Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody -GA101. Mol Cancer Ther. 2011 Jan;10(1):178-85. [3]. Herting F, et al. Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab(GA101) in combination with chemotherapy in xenograft models of human lymphoma. Leuk Lymphoma. 2014 Sep;55(9):2151-5160.