A Phase 2, Double-Blind, Placebo-Controlled Trial of Rituximab + Galiximab Vs Rituximab + Placebo In Advanced Follicular Non-Hodgkin's Lymphoma (NHL)

Abstract

AbstractAbstract 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 1Demographics and Baseline Disease Characteristics, Galiximab Clinical StudyR+G Group(N = 175)R+P Group(N = 162)Total(N = 337)Age:≤60 years53%57%55%Median59.0 y59.0 y59.0 yMin, Max27, 91 y33, 88 y27, 91 yMale46%52%49%Time since diagnosis:Median5.05 y5.26 y5.10 yMin, Max0.6, 24.0 y0.2, 24.8 y0.2, 24.8 yDisease stage at study entry:Stage III/IV76%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:≤262%59%61%>238%41%39%Tumor bulk:Largest lesion >7 cm15%15%15%Rituximab naive35%30%32% [Display omitted] Disclosure:McKinney:Biogen Idec: Employment. Ruffner:Biogen Idec: Employment. Wilson:Biogen Idec: Employment. Whiteley:Biogen Idec: Employment.