Last week the FDA announced approval for obinutuzumab (Gazyva) in combination with chlorambucil for the treatment of patients with previously untreated CLL. Obinutuzumab is the first designated “Breakthrough Therapy” to be granted FDA approval, receiving a priority review through its demonstration of “significant improvement” in safety or effectiveness over available therapies.
Obinutuzumab is a 3rd generation type II anti-CD20 antibody. Acting as an immunomodulator, obinutuzumab selectively binds to the extracellular domain of the human CD20 antigen on malignant human B cells.
This “significant improvement” was demonstrated in a phase III study. Patients treated with a combination of obinutuzumab and chlorambucil experienced significant improvement in progression free survival, increasing to an average of 23 months, compared to 11 months for chlorambucil therapy.
The FDA press release can be seen here. Further information regarding CLL clinical trials at Weill Cornell Medical College can be found here.
By Peter Martin, MD
Rituximab is a chimeric (human-mouse) monoclonal antibody directed against the protein CD20 on the surface of B-lymphocytes and most B-cell lymphomas. Several clinical trials have demonstrated that rituximab can increase response rates, prolong remissions, and improve survival among patients with various B-cell lymphomas and is an FDA-approved drug. Interestingly, rituximab was developed during an era when our understanding of how monoclonal antibodies might work was relatively naïve. Obinutuzumab (GA101) is a newer generation anti-CD20 antibody that has undergone significant engineering to capitalize on new knowledge. In preclinical testing, GA101 appeared to work better than rituximab. Three clinical trials evaluating GA101 in patients with follicular lymphoma were presented at the American Society of Hematology (ASH) meeting this year.
Dr. Gilles Salles presented the results of a phase I/II study performed in France, in which patients with indolent non-Hodgkin lymphoma (mostly follicular lymphoma). In phase I of the study, patients were treated with escalating doses of GA101, while in phase 2, patients were randomized between two dose levels (high-dose and low-dose). Most patients had received prior rituximab. Overall, GA101 appeared to be well tolerated, with mild infusion reactions being the most common side effect. The results were encouraging, particularly in the high-dose group, but will need to be confirmed with a larger study and longer follow-up.
Dr. John Radford presented the results of the international GAUDI study, which evaluated the safety and efficacy of combining GA101 with CHOP or FC chemotherapy in patients with previously treated follicular lymphoma. Continue reading “Obinutuzumab (GA101), a New Generation Rituximab”