The first clinical trial to directly compare rituximab (Rituxan? and MabThera?; Roche/Genentech) with the new anti-CD20 monoclonal antibody obinutuzumab for the treatment of relapsed non-Hodgkin lymphoma (NHL) has shown higher response rates for patients treated with the novel therapy.

Results of a randomized phase II trial comparing obinutuzumab, also known as GA101, with rituximab in patients with relapsed CD20+ indolent B-cell non?Hodgkin lymphoma will be presented at the 53rd Annual Meeting of the American Society of Hematology being held in San Diego, December 10 – 13, 2011.

Key molecular features
NHL survival rates have increased dramatically in the last several decades because of such proven and effective targeted therapies as rituximab that aim directly at the key molecular features of the disease. Despite advances in NHL treatment, hematologists continue to be challenged by drug resistance and disease relapses among their patients. Obinutuzumab, a glycoengineered, fully humanized IgG1 monoclonal antibody,is a new investigational therapy and the first type II bio-engineered monoclonal antibody specifically targeting CD20 (a prominent lymphoma biomarker) to be studied for use in NHL. Early research with GA101 has shown potential anti-lymphoma activity, but no studies have compared the results against current clinical options directly.

Protocol
To compare the efficacy and safety of GA101 versus rituximab in patients with relapsed NHL, an international Phase II clinical trial was undertaken measuring overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety outcomes among patients on both treatments. A total of 175 patients were randomized to receive four weekly injections of either GA101 or rituximab with response to treatment assessed between 28 and 42 days after the last dose. Those patients who responded to treatment received ongoing doses of GA101 or rituximab every two months for up to two years.

Higher response rates
After a complete assessment by both investigators and an independent radiology review, trial data revealed that treatment with GA101 resulted in higher response rates in patients compared to treatment with rituximab. The ORR for GA101 was 33.3% vs. 44.6% for rituximab, and the complete remission (or unconfirmed complete remission) rate in the GA101 arm was 12.2% compared to 5.3% for rituximab.

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Well tolerated
Overall, GA101 was well tolerated by most study participants. Although patients on GA101 treatment had a higher rate of infusion reactions, which are a common complication of treatment with monoclonal antibodies, they were generally considered mild and did not result in significant differences in treatment discontinuation. A greater number of patients in the rituximab arm experienced severe adverse events during the four-week induction period (nine patients vs. five GA101 patients). Severe adverse events in GA101 patients included infusion reactions, neutropenia with fever, pleural effusion (a build-up of fluid in the lung tissue), and kidney stones. Finally, more rituximab-treated patients than GA101-treated patients discontinued therapy during the induction period.

Promising efficacy
?This is the first head-to-head trial of a novel anti-CD20 monoclonal antibody, GA101, against rituximab and we are encouraged to see a trend toward higher response rates without appreciable differences in safety,? said lead author Laurie H. Sehn, MD, MPH, Clinical Associate Professor in the Division of Medical Oncology at the University of British Columbia and the British Columbia Cancer Agency, Center for Lymphoid Cancer in Vancouver, Canada. ?Given the promising efficacy of this drug, definitive Phase III studies evaluating its benefit are warranted and are currently underway.?

Dr. Sehn will present this study in an oral presentation on Monday, December 12, at 8:00 a.m. PST.

For more information:

Title: Randomized Phase II Trial Comparing GA101 (Obinutuzumab) with Rituximab in Patients with Relapsed CD20+ Indolent B-Cell Non?Hodgkin Lymphoma: Preliminary Analysis of the GAUSS Study
Abstract: 269
Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Lymphoma – Therapy with Biologic Agents, excluding Pre-Clinical Models: Novel Biologic Approaches to Indolent Lymphoma
When: Monday, December 12, 2011: 7:00 AM
Where: Ballroom 20A (San Diego Convention Center)

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