Comparison of Single Agent GA101 In Japanese and European Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (B-NHL) – Results From Two Phase I Studies

Abstract 4921 Background: Most studies regarding the chimeric anti-CD20-antibody rituximab have reported no ethnic differences including response or safety in B-NHL. GA101 is the first type II, glycoengineered and humanized anti-CD20 monoclonal antibody to enter clinical trials. Results in B-NHL patients have previously been reported from three phase I studies, conducted in Europe, Canada and Japan (Salles 2008, 2010, Sehn 2009, Tobinai 2010), and all have demonstrated good tolerability along with promising activity, with a safety profile largely similar to rituximab when compared to historical rituximab data. Here we report a comparison of the phase I studies BO20999 and JO21900, conducted in Europe and Japan, respectively, to analyze any potential ethnic differences in safety/efficacy. Both studies were conducted in patients with relapsed/refractory B-NHL, with the majority of patients being of indolent histology and both studies used identical drug administration and response assessment schedules. Methods: In both studies GA101 was administered IV as monotherapy (as an absolutely flat dose) on days 1, 8 and 22, and then every 3 wks, for a total of 9 infusions. The dose was escalated using a 3+3 design, with study JO21900 starting at a higher dose of 200/400mg (with doses up to 2,000mg, a dose level judged safe and well tolerated in BO20999 (doses ranging from 50-2, 000mg). Patient and disease characteristics, prior treatments, response rates and safety parameters from both studies were compared. Given the small sample sizes, heterogeneity, the dose-escalation design and the cross-trial comparison, no formal statistical analysis was applied. Results: Patient age and other baseline parameters were substantially similar between the two studies (Table 1). The safety profiles in both studies were comparable, with the most common AEs being infusion-related reactions (86% BO20999; 100% JO21900) of grade 1–2 mainly associated with the first infusion and decreasing with subsequent infusions. Incidence of SAEs were similar (BO20999 [n=4], JO21900 [n=2]). Importantly, no dose-limiting toxicities and no dose reductions were observed in either study. No patients with aggressive histology were enrolled into study JO21900, and Japanese patients were less heavily pretreated (median of 1 vs 4 prior treatments for European patients) and no Japanese patient had received prior autologous stem cell transplant. End of treatment response rates were slightly higher in Japanese study than those in the European study (Table 1). GA101 plasma drug concentrations in both studies were comparable, with the observation of a large inter-patient variability, however, a dose-dependent increase in mean plasma concentrations, increasing with dose, was observed in both studies. Conclusion: These clinical, safety and pharmacokinetic results from two phase I studies suggest that there appears to be no apparent differences between Japanese and European patients with respect to the safety or efficacy of GA101 monotherapy in indolent B-NHL patients, although analyses on larger datasets would be required to confirm these initial results. The slightly higher response rates observed in Japanese patients may be attributable to the small sample size, and a less heavily pre-treated population that comprised of patients solely of indolent histology only. Disclosures: Morschhauser: Roche: Consultancy, Honoraria. Cartron: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hatake: Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding. Wenger: Roche: Employment. Birkett: Roche: Employment. Oya: Chugai Pharmaceutical Co., Ltd.: Employment. Nishima: Chugai Pharmaceutical Co., Ltd.: Employment. Salles: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.