A supplemental biologics license application for obinutuzumab (Gazyva) in combination with chemotherapy, followed by obinutuzumab alone, has been granted a priority review by the FDA for the first-line treatment of patients with follicular lymphoma.
Sandra Horning, MD
A supplemental biologics license application (sBLA) for obinutuzumab (Gazyva) in combination with chemotherapy, followed by obinutuzumab alone, has been granted a priority review by the FDA for the first-line treatment of patients with follicular lymphoma, according to Genentech, the manufacturer of the therapy.
The sBLA is based on data from the phase III GALLIUM study, in which combining obinutuzumab with chemotherapy in the first-line setting reduced the risk of disease progression or death by 32% versus rituximab plus chemotherapy in patients with follicular lymphoma.1 Under the Prescription Drug User Fee Act, the FDA is scheduled to make a final approval decision on or before December 23, 2017.
“Follicular lymphoma becomes harder to treat each time it returns, and the goal of initial treatment is to prevent the cancer from progressing for as long as possible,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a press release. “Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible.”
The international phase III GALLIUM study included 1401 treatment-naive patients with indolent non-Hodgkin lymphoma, of whom 1202 had follicular lymphoma. Patients with follicular lymphoma were aged ≥18 years, had grade I to IIIa disease, and an ECOG performance status ≤2.
Patients were randomized to obinutuzumab plus chemotherapy, followed by obinutuzumab alone (n = 601), or rituximab plus chemotherapy, followed by rituximab alone (n = 601). The chemotherapy regimens used were CHOP, CVP, or bendamustine, based on the discretion of the physicians at each study location.
Patients specifically received rituximab at 375mg/m2 on day 1 of each cycle or obinutuzumab at 1000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles, for either eight 21-day cycles (CHOP and CVP) or six 28-day cycles (bendamustine). Among patients randomized to chemotherapy, 57.1%, 33.1%, and 9.8%, received bendamustine, CHOP, and CVP, respectively.
The primary endpoint of the study was progression-free survival (PFS). Secondary outcome measures included response rate, overall survival (OS), disease-free survival, and safety. The study was unblinded per the recommendation of an independent data monitoring panel in January 2016 after a preplanned interim efficacy analysis.
At a median follow-up of 41.1 months, the hazard ratio (HR) for PFS by investigator assessment was 0.68 (95% CI, 0.54-0.87;P= .0016). Per independent review, the HR for PFS was 0.72 (95% CI, 0.56-0.93; P = .0018). The median PFS has not been reached yet in either treatment arm.
Safety data from the 41.1-month follow-up showed that the most common grade 3/5 adverse events that occurred more often in the obinutuzumab arm compared to the rituximab arm were neutropenia (46.7% vs 39.5%), infections (20.3% vs 16.4%), infusion-related reactions (12.4% vs 6.7%), thrombocytopenia (6.1% vs 2.7%), second malignancies (4.7% vs 2.7%), and cardiac events (3.9% vs 2.8%).
Data from a median follow-up of 34.5 months were presented at the 2016 ASH Annual Meeting.2 Those results showed that the 3-year PFS rate was 80% in the obinutuzumab arm versus 73.3% in the rituximab arm. The 3-year PFS rate was 81.9% in the obinutuzumab arm versus 77.9% in the rituximab arm.
The HR for OS was 0.75 (95% CI, 0.49-1.17;P= .21). The 3-year OS rates were 94% versus 92.1% in the obinutuzumab versus the rituximab arms, respectively.
In the obinutuzumab arm, the overall response rate was 88.5% versus 86.9% in the rituximab cohort. The complete remission rates were 19.5% versus 23.8% and the partial remission rates were 69.1% versus 63.1%, respectively. Ninety-two percent of patients in the obinutuzumab arm achieved MRD-negativity in the blood and/or bone marrow, compared with 84.9% in the control arm (P= .0041).
Obinutuzumab is a glycoengineered antibody against CD20. Through the glycoengineering process, sugar molecules are removed from immune-effector antibody cells in the posttranslational setting, significantly impacting antigen binding and function. Specifically, obinutuzumab is designed to lack fucose molecules.
The FDA previously approved obinutuzumab for use in combination with bendamustine for patients with follicular lymphoma who have received prior therapy.