Obinutuzumab iNHL Trial Ends Early, Genentech to File for FDA and EMA Approval

Genentech, the manufacturer of obinutuzumab, plans to file for FDA and EMA approval after a phase III study of the anti-CD20 agent in indolent non-Hodgkin lymphoma (iNHL) garnered positive results in an interim analysis.

Sandra Horning, MD

Genentech, the manufacturer of obinutuzumab, will file for FDA and EMA approval after a phase III study of the anti-CD20 agent in indolent non-Hodgkin lymphoma (iNHL) garnered positive results in an interim analysis.

Obinutuzumab (Gazyva) was the subject of the phase III GADOLIN study, which compared bendamustine alone with obinutuzumab plus bendamustine followed by obinutuzumab in patients with iNHL refractory to rituximab (Rituxan).

It was found, during an independent panel, that the multicenter, open-label 43-patient GADOLIN study met its primary endpoint: the obinutuzumab arm had a significant improvement in progression-free survival (PFS).

“GADOLIN is the first of our pivotal phase III studies of Gazyva to be completed in the non-Hodgkin lymphoma setting, building on the positive results we have seen in chronic lymphocytic leukemia,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Roche, in a statement.

Patients in the experimental arm received bendamustine (90 mg/m2IV on days 2 and 3 of cycle 1, and days 1 and 2 of cycles 2-6) plus 6 cycles of obinutuzumab (1000 mg IV on days 1, 8, and 15 of cycle 1, and day 1 of cycles 2-6) followed by obinutuzumab every 2 months until disease progression for a maximum of 2 years. In the comparator group, patients received 6 cycles of bendamustine monotherapy (120 mg/m2IV on days 1 and 2 of cycles 1-6).

The cycle length for both treatment arms was 28 days. In addition to the primary PFS endpoint, secondary endpoints included overall survival and response rates.

Genentech also plans to present the GADOLIN data at an upcoming scientific meeting and file for regulatory approval with the FDA and EMA.

“We are delighted that this study could be evaluated early due to the strength of its data, which we believe supports Gazyva’s potential in combination with bendamustine for people whose Rituxan-based therapy failed to adequately control their disease,” said Horning.

Promising data for obinutuzumab in relapsed/refractory iNHL from the phase II GAUGUIN trial were previously published in theJournal of Clinical Oncology (J Clin Oncol.2013;31(23):2920-2926).

That trial included 40 iNHL patients, 34 of whom had follicular lymphoma. Thirty-eight patients had received rituximab and 22 were refractory to the drug. Patients received 8 cycles of obinutuzumab at 400 mg on days 1 and 8 of cycle 1 and also on day 1 of cycles 2 to 8 (400/400 mg) or 1600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8 (1600/800 mg).

The overall response rate was 55% in the 1600/800-mg group and 17% in the 400/400-mg group. Nine percent of the responses in the higher dose group were complete responses, as compared with zero for the lower-dose arm.

The median PFS was 11.9 months and 6.0 months, respectively. Seventy-three percent of patients had infusion-related reactions (IRRs), which was the most frequently reported adverse event. Two patients, both in the 1600/800-mg group, had grade 3/4 IRRs. According to the researchers, there were no serious IRRs, and none resulted in a patient withdrawal from the study.

When Genentech files for regulatory approval for obinutuzumab in iNHL, it will be seeking a second indication for the drug. Obinutuzumab is currently approved by the FDA for use in combination with chlorambucil as a first-line treatment for patients with chronic lymphocytic leukemia.