The FDA has accepted a supplemental Biologics License Application (sBLA) and granted Priority Review for obinutuzumab in combination with chemotherapy followed by obinutuzumab alone for people with previously-untreated follicular lymphoma.
The sBLA is based on results of the GALLIUM study, which is the first phase III study in previously-untreated follicular lymphoma to show superior progression-free survival (PFS) over rituximab-based treatment, the current standard of care. Adverse events (AEs) with either obinutuzumab or rituximab were consistent with those seen in previous studies.
The FDA is expected to make a decision on approval under Priority Review by Dec. 23, 2017. Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention, or diagnosis of a serious disease. Additional submissions of the GALLIUM data to health authorities around the world are ongoing.
GALLIUM (NCT01332968) is a global phase III open-label, multicenter, randomized two-arm study examining the efficacy and safety of obinutuzumab plus chemotherapy followed by obinutuzumab alone for up to 2 years, as compared head-to-head against rituximab plus chemotherapy followed by rituximab alone for up to 2 years. Chemotherapies used were CHOP, CVP, or bendamustine and were selected by each participating study site prior to beginning enrollment.
GALLIUM included 1,401 patients with previously untreated indolent non-Hodgkin lymphoma (iNHL), of which 1,202 patients had follicular lymphoma. The primary endpoint of the study was investigator-assessed PFS in patients with follicular lymphoma, with secondary endpoints including PFS assessed by independent review committee (IRC) in patients with follicular lymphoma, PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival, and safety. The study is being conducted in cooperation with the GLSG (Germany), the East German Study Group Hematology and Oncology (OSHO; Germany), and the NCRI (United Kingdom).
Results after a follow-up period of 41.1 months showed:
* Obinutuzumab-based treatment reduced the risk of disease worsening or death (PFS, as assessed by investigator) by 32 percent compared to rituximab-based treatment (HR=0.68; 95% CI 0.54-0.87; p=0.0016).
* IRC-assessed PFS was consistent with investigator-assessed PFS. As assessed by IRC, obinutuzumab-based treatment reduced the risk of disease worsening or death by 28 percent compared to rituximab-based treatment (HR=0.72; 95% CI 0.56-0.93; p=0.0018). Median PFS has not yet been reached in either treatment arm.
* The most common grade 3-5 AEs that occurred more often in the obinutuzumab arm compared to the rituximab arm were low white blood cell count (neutropenia, 46.7% vs. 39.5%), infections (20.3% vs. 16.4%), infusion-related reactions (IRRs, 12.4% vs. 6.7%), low platelet count (thrombocytopenia, 6.1% vs. 2.7%), new tumors (second malignancies, 4.7% vs. 2.7%), and cardiac events (3.9% vs. 2.8%).
GALLIUM is the third positive phase III study for obinutuzumab, following the CLL11 study in patients with previously-untreated chronic lymphocytic leukemia and the GADOLIN study in patients with iNHL whose disease progressed during or within 6 months of prior rituximab-based therapy.