The first results from CLL11, a phase III study of the investigational medicine Obinutuzumab ( GA101; Gazyva ) were presented. The CLL11 study compared the combination of either GA101 or Rituximab ( MabThera; Rituxan ) and Chlorambucil, a standard chemotherapy, to Chlorambucil alone in chronic lymphocytic leukemia ( CLL ).
Chronic lymphocytic leukemia is one of the most common forms of blood cancer and in 2013, it is expected that there will be nearly 5,000 deaths from CLL in the United States.
The CLL11 study included elderly people with previously untreated chronic lymphocytic leukemia who were often not able to tolerate existing aggressive treatment options.
Obinutuzumab combined with Chlorambucil demonstrated a significant 86% reduction in the risk of disease progression, relapse or death. Additionally, the length of time during which people lived without their disease worsening ( median progression-free survival, PFS ) was more than doubled ( 23 months compared to 10.9 months, hazard ratio, HR=0.14; p less than 0.0001 ) when compared to Chlorambucil alone.
Obinutuzumab is the first type II anti-CD20 medicine that is glycoengineered, which means specific sugar molecules in GA101 were modified ( using GlycoMAb technology ) to change its interaction with the body's immune cells with the goal of helping the immune system remove cancer cells from the body. In addition, as a type II anti-CD20 antibody, Obinutuzumab binds to CD20 with the aim of killing cancerous cells directly.
CLL11 is a phase III, multicenter, open-label, randomized three-arm study investigating the safety and efficacy profile of either Obinutuzumab added to Chlorambucil or Rituximab added to Chlorambucil compared to Chlorambucil alone in 781 previously untreated people with CLL and comorbidities ( 589 patients are included in this analysis and an additional 192 patients have been enrolled to enable the forthcoming direct comparison of Obinutuzumab versus Rituximab both in combination with Chlorambucil ).
The primary endpoint of the study was progression-free survival ( PFS ) with secondary endpoints including overall response rate ( ORR ), overall survival ( OS ), disease-free survival ( DFS ), minimal residual disease ( MRD ) and safety profile.
Specifically, the CLL11 trial data showed the following: the addition of Obinutuzumab to Chlorambucil led to a statistically significant reduction in the risk of disease progression or death of 86% ( HR=0.14; p less than 0.0001 ); the median PFS improved by more than a year from 10.9 months for Chlorambucil alone to 23 months for Obinutuzumab plus Chlorambucil; the addition of Rituximab to Chlorambucil significantly reduced the risk of disease progression or death during study follow-up by 68% ( HR=0.32; p less than 0.0001); median PFS was 10.8 months for Chlorambucil compared to 15.7 months for Rituximab plus Chlorambucil.
No new safety signals were detected for either Obinutuzumab or Rituximab. The most common grade 3-4 adverse events (AEs ) for Obinutuzumab were infusion-related reactions ( IRRs ) and neutropenia. The incidence and severity of IRRs decreased dramatically after the first infusion and no serious IRRs have been reported beyond the first infusion. ( Xagena )
Source: Genentech, 2013