Laurie H. Sehn, MD, MPH
Treatment with a novel CD20 monoclonal antibody, GA101 (obinutuzumab), in patients with relapsed non-Hodgkin lymphoma (NHL) resulted in higher response rates as compared with rituximab, in a preliminary analysis of the Phase II randomized GAUSS study presented at the 53rd Annual Meeting of the American Society of Hematology.
“This is the first head-to-head trial of GA101 against rituximab in patients with relapsed indolent NHL. GA101 demonstrated promising efficacy with a trend towards higher response rates, without appreciable differences in safety,” said Laurie H. Sehn, MD, MPH, associate professor of medicine atthe British Columbia Cancer Agency in Vancouver.
GA101 is the first type II glycoengineered CD20 monoclonal antibody in Phase II/III clinical trials for NHL. GA101 single-arm clinical studies have demonstrated responses in patients with relapsed/refractory NHL, as well as chronic lymphocytic leukemia, but this study is the first direct comparison with rituximab.
Patients with relapsed indolent NHL requiring therapy after a prior complete response (CR) or unconfirmed complete response (CRu) to a rituximab-containing regimen were eligible. A total of 175 patients (149 follicular [FL] and 26 nonfollicular indolent NHL) were randomized to receive 4 weekly infusions (Days 1, 8, 15, 22) of either GA101 or rituximab. Patients had received an average of 2 prior lines of therapy (99% with rituximab).
Their response was assessed 28 to 42 days after the last induction dose. Patients without evidence of progression following induction therapy received ongoing treatment with GA101 or rituximab every 2 months for up to 2 years at the same dose. The groups were balanced although at baseline patients receiving GA101 had a larger volume of disease.
Trend Toward Greater Response With GA101
The primary efficacy analysis was conducted in the FL population (n=149) at the end of induction. Based on investigator assessment, the objective response rate (ORR) for GA101 was 44.6% versus 33.3% for rituximab, amounting to 11.3% more responses with the novel agent (P
=0.08). CR/CRu was observed in 12.2% versus 5.3%, respectively, Sehn reported.
The best overall response in the FL population was CR/Cru for 35.1% of the GA101 group and 18.7% of the rituximab group.
Sehn mentioned that the study was not powered to show superiority of GA101 over rituximab, but to provide a general comparison of its efficacy.
Safety analysis in the overall population revealed no new safety signals. There were more infusion-related reactions with GA101, 74% versus 51% with rituximab, including 11% and 6% as grade 3 or 4. Cough was also more frequent in this arm, 21% versus 6%. The infusion-related reactions generally occurred during the first infusion and diminished in frequency and severity with subsequent infusions, she added.
“Based on these data, we believe that Phase III trials to truly test the efficacy of this agent are warranted, and they are now underway,” she said. GA101 is under study in Phase III trials in combination with chemotherapy, in patients with NHL, diffuse B-cell lymphoma, and chronic lymphocytic leukemia.
Jane Winter, MD, professor of medicine at Northwestern University Feinberg School of Medicine, Chicago, Illinois commented at a press briefing, “These findings show how our new technologies are providing us with new tools that are, hopefully, better than we have had before. Sehn showed the benefit of engineering an antibody, rather than serendipitously finding one that is effective.”>>>Return to the main conference coverage page.