Abstract 428

Background:

Galiximab is a primatized chimeric monoclonal antibody directed against CD80, an immunoregulatory protein normally expressed on antigen presenting cells and T cells, as well as in B-cell NHL, Hodgkin lymphoma, multiple myeloma, and certain leukemias. Galiximab directly mediates antibody-dependent cell-mediated cytotoxicity against tumor cells in vitro. In ex vivo assays, galiximab can act on non-malignant cells to modulate immune signaling within the tumor microenvironment.

Methods:

Subjects with relapsed or refractory, Grade I-IIIa, follicular NHL in relapse following treatment with at least 1 chemotherapy regimen, and who were not refractory to rituximab were randomized to rituximab (375 mg/m2) plus galiximab (500 mg/m2; R+G) or rituximab plus placebo (R+P) and treated on Days 1, 8, 15, and 22. Randomization and primary efficacy analyses were stratified by age (≤60 vs >60), rituximab exposure (rituximab naïve vs non-naïve), and baseline tumor bulk (diameter of largest lesion ≤7 cm vs >7 cm). Primary endpoint of progression-free survival (PFS) was analyzed using a stratified log-rank test.

Results:

This study, originally planned as a Phase 3 confirmatory study, was terminated early due to changes in standard of care and converted to a Phase 2 study. Therefore, interpretation of p-values was focused on assessing the potential of these data to support subsequent Phase 2 and Phase 3 studies. At study termination, 337 subjects were randomized (175 R+G and 162 R+P) with median follow-up of 13.8 months. Demographics and disease characteristics were well balanced across the 2 treatment groups (Table 1). The addition of galiximab to rituximab reduced the hazard for disease progression or death by 26% (hazard ratio [HR] = 0.738; 95% confidence interval [CI] [0.543, 1.002]; p = 0.050) compared to the R+P group. Kaplan-Meier median PFS was 12.0 months (95% CI [9.0, 14.7]) for R+G and 9.0 months (95% CI [8.9, 10.5]) for R+P. Overall response rate was 51% for R+G vs 48% for R+P (p = 0.455) and complete response was 20% for R+G and 15% for R+P (p = 0.251). Consistency in treatment effect was seen across patient subgroups (Figure 1). A trend toward a larger PFS effect was observed in patients who were rituximab-naïve, had bulky tumor (largest lesion >7 cm), had lactate dehydrogenase (LDH) >1 × upper limit of normal, or had bone marrow involvement at study entry. There were 10 deaths in R+G vs 17 deaths in R+P; HR = 0.549 based on a stratified log-rank analysis (95% CI [0.248, 1.217]; p = 0.135). No substantial difference was observed between groups for Grade 3/4 adverse events (AEs) or serious AEs, and there were no treatment-related deaths in either group. Incidence of AEs was ≥3% higher in the R+G vs R+P group for the following: pyrexia (18% vs 11%), headache (13% vs 7%), cough (10% vs 6%), upper respiratory infection (8% vs 4%), insomnia (8% vs 4%), neutropenia (6% vs 3%), muscle spasms (5% vs <1%), and oropharyngeal pain (4% vs 1%). Anti-galiximab antibodies were not detected in 169 subjects treated with galiximab who were tested while on study.

Conclusions:

Galiximab in combination with rituximab demonstrated a trend toward an improved PFS compared with rituximab alone and was well tolerated in subjects with relapsed or refractory follicular NHL.

Table 1.

Demographics and Baseline Disease Characteristics, Galiximab Clinical Study

R+G Group(N = 175)R+P Group(N = 162)Total(N = 337)
Age:    
    ≤60 years 53% 57% 55% 
    Median 59.0 y 59.0 y 59.0 y 
    Min, Max 27, 91 y 33, 88 y 27, 91 y 
Male 46% 52% 49% 
Time since diagnosis:    
    Median 5.05 y 5.26 y 5.10 y 
    Min, Max 0.6, 24.0 y 0.2, 24.8 y 0.2, 24.8 y 
Disease stage at study entry:    
    Stage III/IV 76% 77% 77% 
FLIPI risk group:    
    Low/Intermediate (0-2) 67% 63% 65% 
    High (3-5) 32% 33% 32% 
    Missing <1% 4% 2% 
Prior lymphoma therapies:    
    ≤2 62% 59% 61% 
    >2 38% 41% 39% 
Tumor bulk:    
    Largest lesion >7 cm 15% 15% 15% 
Rituximab naive 35% 30% 32% 
R+G Group(N = 175)R+P Group(N = 162)Total(N = 337)
Age:    
    ≤60 years 53% 57% 55% 
    Median 59.0 y 59.0 y 59.0 y 
    Min, Max 27, 91 y 33, 88 y 27, 91 y 
Male 46% 52% 49% 
Time since diagnosis:    
    Median 5.05 y 5.26 y 5.10 y 
    Min, Max 0.6, 24.0 y 0.2, 24.8 y 0.2, 24.8 y 
Disease stage at study entry:    
    Stage III/IV 76% 77% 77% 
FLIPI risk group:    
    Low/Intermediate (0-2) 67% 63% 65% 
    High (3-5) 32% 33% 32% 
    Missing <1% 4% 2% 
Prior lymphoma therapies:    
    ≤2 62% 59% 61% 
    >2 38% 41% 39% 
Tumor bulk:    
    Largest lesion >7 cm 15% 15% 15% 
Rituximab naive 35% 30% 32% 
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Figure 1.
Figure 1. Progression-Free Survival by Patient Subgroup, Galiximab Clinical Study Solid line represents the hazard ratio observed in the primary analysis.
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Progression-Free Survival by Patient Subgroup, Galiximab Clinical Study Solid line represents the hazard ratio observed in the primary analysis.

Figure 1.
Figure 1. Progression-Free Survival by Patient Subgroup, Galiximab Clinical Study Solid line represents the hazard ratio observed in the primary analysis.
View largeDownload slide

Progression-Free Survival by Patient Subgroup, Galiximab Clinical Study Solid line represents the hazard ratio observed in the primary analysis.

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Disclosure:

McKinney:Biogen Idec: Employment. Ruffner:Biogen Idec: Employment. Wilson:Biogen Idec: Employment. Whiteley:Biogen Idec: Employment.

Topics:
follicular lymphoma, rituximab, neoplasms, antibodies, adverse event, bone marrow involvement, cd80 antigens, chemotherapy regimen, complete remission, cough

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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