Phase I study of obinutuzumab (GA101) in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

Abstract

As CD20 has become an established target for treating B-cell malignancies, there is interest in developing anti-CD20 antibodies with different functional activity from rituximab that might translate into improved efficacy. Obinutuzumab (GA101) is a glycoengineered, humanized type II anti-CD20 monoclonal antibody that has demonstrated superior activity to type I antibodies in preclinical studies and is currently being investigated in phase III trials. In this phase I dose-escalating study in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the primary endpoint was to characterize the safety of GA101; secondary endpoints were efficacy, pharmacokinetics and pharmacodynamics. Patients received up to nine doses of GA101 with up to 52 weeks' follow up. Most adverse events were grade 1 or 2 infusion-related reactions, and 10 grade 3/4 adverse events occurred. No dose-limiting toxicities were observed and the maximum tolerated dose was not identified. Out of 12 patients, 7 responded (end-of-treatment response rate 58%), with 2 complete responses and 5 partial responses. Responses were observed from low to high doses, and no dose-efficacy relationship was observed. B-cell depletion occurred in all patients after the first infusion and was maintained for the duration of treatment. Serum levels of GA101 increased in a dose-dependent fashion, although there was inter-patient variability. This phase I study demonstrated that GA101 has an acceptable safety profile and offers encouraging activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

• Authors: Michinori Ogura, Kensei Tobinai, Kiyohiko Hatake, Toshiki Uchida, Tatsuya Suzuki, Yukio Kobayashi, Masakazu Mori, Yasuhito Terui, Masahiro Yokoyama, Tomomitsu Hotta
• Journal: Cancer science (Cancer Sci) Vol. 104 Issue 1 Pg. 105-10 (Jan 2013) ISSN: 1349-7006 [Electronic] England
• PMID: 23046388 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Japanese Cancer Association.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antigens, CD20
• Antineoplastic Agents
• obinutuzumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (adverse effects, pharmacokinetics, therapeutic use)
• Antigens, CD20 (immunology)
• Antineoplastic Agents (adverse effects, pharmacokinetics, therapeutic use)
• Female
• Humans
• Japan
• Lymphoma, B-Cell (drug therapy)
• Male
• Middle Aged
• Recurrence
• Young Adult