Date: 2016-05-27
Type of information: Results
phase: 3
Announcement: results
Company: Roche (Switzerland)
Product: Gazyva®/Gazyvaro® (obinutuzumab)
Action
mechanism: monoclonal antibody. Obinutuzumab is a glycoengineered, fully humanized IgG1 monoclonal antibody with potential antineoplastic activity. Obinutuzumab, a third generation type II anti-CD20 antibody, selectivity binds to the extracellular domain of the human CD20 antigen on malignant human B cells. The Fc region carbohydrates of the antibody, enriched in bisected non-fucosylated glycosylation variants, contribute to its higher binding affinity for human FcgammaRIII receptors compared to non-glycoengineered antibodies, resulting in enhanced antibody-dependent cellular cytotoxicity (ADCC) and caspase-independent apoptosis. In addition, modification of elbow hinge sequences within the antibody variable framework regions may account for the strong apoptosis-inducing activity of R7159 upon binding to CD20 on target cells. Preclinical studies demonstrate that GA101 induces significant B-cell depletion in peripheral blood as well as in lymphoid tissue. It also mediates high antitumor activity in preclinical NHL studies, both as a single agent and in conjunction withchemotherapy.
Genentech is investigating this agent with Biogen Idec.
Disease: non-Hodgkin's lymphoma
Therapeutic area: Cancer - Oncology
Country: Australia, Belgium, Brazil, Canada, China, Czech Republic, Finland, France, Germany, Hungary, Israel, Italy, Japan, Russian Federation, Spain, Sweden, Taiwan, UK, USA
Trial
details: GALLIUM is an open-label, randomized study evaluating the efficacy and safety of obinutuzumab (RO5072759) in combination with chemotherapy compared to MabThera®/Rituxan® (rituximab) with chemotherapy followed by obinutuzumab or MabThera®/Rituxan® maintenance in patients with untreated advanced indolent non-Hodgkin's lymphoma. After the end of the induction period, patients achieving response (CR or PR) will go on to a maintenance period thereby continuing on their randomized antibody treatment alone every 2 months until disease progression for a total of 2 years. Anticipated time on study treatment is up to approximately 2.5 years. After maintenance or observation patients will be followed for 5 years until progression. After progression, patients will be followed for new anti-lymphoma therapy and overall survival until the end of the study. GALLIUM included 1401 patients with previously untreated indolent non-Hodgkin lymphoma (iNHL), of which 1202 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), PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival (OS), disease-free survival (DFS) and safety. The GALLIUM study is being conducted in cooperation with the German Low Grade Lymphoma Study Group (GLSG; Germany), the East German Study Group Hematology and Oncology (OSHO; Germany) and the National Cancer Research Institute (NCRI; United Kingdom).(NCT01332968)
Latest
news: * On May 27, 2016, Roche announced positive results from the pivotal phase III GALLIUM study in people with previously untreated follicular lymphoma, the most common type of indolent (slow-growing) non-Hodgkin lymphoma (iNHL). The study compared the efficacy and safety of Gazyva®/Gazyvaro® (obinutuzumab) plus chemotherapy (CHOP, CVP or bendamustine) followed by Gazyva®/Gazyvaro® alone, head-to-head with MabThera®/Rituxan® (rituximab) plus chemotherapy followed by MabThera®/Rituxan® alone. Results from a pre-planned interim analysis showed that Gazyva®/Gazyvaro®-based treatment significantly reduced the risk of disease worsening or death (progression-free survival; PFS, as assessed by investigator) compared to MabThera®/Rituxan®-based treatment. Adverse events with either Gazyva®/Gazyvaro® or MabThera®/Rituxan® were consistent with what was seen in previous clinical trials when each was combined with various chemotherapies. Data from the GALLIUM study will be presented at an upcoming medical meeting and submitted to health authorities for approval consideration.
In the first head-to-head comparison of Gazyva®/Gazyvaro® and MabThera®/Rituxan®, the CLL11 study in people with previously untreated chronic lymphocytic leukaemia and comorbidities, Gazyva®/Gazyvar®o plus chlorambucil significantly extended PFS compared to treatment with MabThera®/Rituxan® plus chlorambucil (median PFS 26.7 months vs. 14.9 months, respectively; HR=0.42; 95% CI, 0.33-0.54; p<0.0001). The most common side effects of Gazyva/Gazyvaro plus chlorambucil were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhoea.
