Obinutuzumab (GAZYVA®)

Agent Description

Obinutuzumab is a humanized anti-CD20 monoclonal antibody of the IgG1 subclass. It recognizes a specific epitope of the CD20 molecule found on B cells. The molecular mass of the antibody is approximately 150 kDa. Obinutuzumab is produced by mammalian cell (CHO) suspension culture. Obinutuzumab was engineered for reduced fucose content as compared to a typical IgG1 produced in CHO cells. Obinutuzumab is a sterile, clear, colorless to slightly brown, preservative-free liquid concentrate for intravenous administration. Obinutuzumab is supplied at a concentration of 25 mg/mL in 1000 mg single-use vials. The product is formulated in 20 mM L-histidine/L-histidine hydrochloride, 240 mM trehalose, 0.02% poloxamer 188. The pH is 6.0.

Mechanism of Action

Obinutuzumab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre B- and mature B-lymphocytes. Upon binding to CD20, obinutuzumab mediates B-cell lysis through (1) engagement of immune effector cells, (2) by directly activating intracellular death signaling pathways (direct cell death), and/or (3) activation of the complement cascade. The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis.

As an antibody with reduced fucose content, obinutuzumab induces greater ADCC activity than rituximab in vitro using human cancer cell lines. Obinutuzumab also demonstrated an increased ability to induce direct cell death when compared to rituximab. Obinutuzumab binds to FcγRIII using purified proteins with a higher affinity than rituximab. Obinutuzumab and rituximab bind with similar affinity to overlapping epitopes on CD20.

Classification

Monoclonal antibody

Molecular Targets

CD20

Monograph

Approved Indications:

Obinutuzumab in combination with chlorambucil, is indicated for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).
Obinutuzumab, in combination with bendamustine followed by obinutuzumab monotherapy, is indicated for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximab-containing regimen.

Package insert: https://www.gene.com/download/pdf/gazyva_prescribing.pdf

Studies of Interest

CLL and Follicular Lymphoma in first-line and relapsed/refractory settings; in combination with novel treatments with potentially complementary mechanism of action
studies to assess the value of achieving MRD (minimal residual disease) negativity.

Information collaborator would like included in investigator proposals

N/A

Genentech supports non-clinical research proposals through a separate mechanism. Please visit https://www.gene.com/gene/reagents-program/reagents-program.jsp if you wish to submit a request for a Genentech agent for non-clinical work.