The phase II portion of the GAUGUIN study found promising activity with the anti-CD20 antibody obinutuzumab in patients with relapsed or refractory indolent NHL.
The phase II portion of the GAUGUIN study found an acceptable dosing schedule and promising activity with the anti-CD20 antibody obinutuzumab in patients with relapsed or refractory indolent non-Hodgkin lymphoma.
“Given that CD20 has proved to be a highly successful target antigen for immunotherapeutic approaches in hematologic malignancies, the development of novel anti-CD20 antibodies with functional activity different from that of rituximab may translate to improved efficacy,” wrote authors led by Gilles A. Salles, MD, PhD, of Hospices Civils de Lyon-Universite de Lyon in France, in the Journal of Clinical Oncology.
In the phase II portion of a phase I/II study, 40 patients were included, 34 of whom had follicular lymphoma; 38 of the patients (95%) had previously been treated with rituximab and 22 were rituximab refractory. Patients were randomized to receive one of two dosing schedules: either 8 cycles of obinutuzumab 400 mg on days 1 and 8 of cycle 1, and on day 1 of cycles 2 to 8 (400/400 mg, 18 patients); or 1,600 mg on days 1 and 8 of cycle 1, and 800 mg on day 1 of cycles 2 to 8 (1600/800 mg, 22 patients).
After treatment, the overall response rate was 17% in the 400/400 mg group, and 55% in the 1600/800 mg group; 9% of the higher-dose group had a complete response, compared with none in the lower-dose group. Among only the rituximab-refractory patients, 5 of 10 patients achieved a response in the 1600/800 group vs only 1 of 12 patients in the 400/400 mg group. Median progression-free survival (PFS) was 11.9 months in the higher-dose group and 6 months in the lower-dose patients.
The most common adverse events were infusion-related, in 73% of patients, but only two patients in the 1600/800 mg group had an infusion-related reaction of grade 3 or 4; no patients withdrew from the study because of such reactions.
“Considering the preclinical data and findings of the present study, the higher-dose is undergoing further development,” the authors wrote, adding that a simplified schedule using 1,000 mg for all cycles with doses on days 1, 8, and 15 of cycle 1 is now moving to phase III testing. The GADOLIN and GALLIUM study are evaluating obinutuzumab in combination with bendamustine and alone vs rituximab as well.
Though the present study was limited by its small size, the investigators saw promise in the higher-dose regimen. “The higher response rates and longer PFS for the 1,600/800-mg dose regimen strongly suggest superiority relative to the 400/400-mg dose,” they wrote.