Updated Results from a Phase II Study of Galiximab (Anti-CD80) in Combination with Rituximab for Relapsed or Refractory, Follicular NHL.

Galiximab is a PRIMATIZED®, anti-CD80, monoclonal antibody with human IgG1 constant regions and macaque variable regions. CD80 is an immune costimulatory molecule that is constitutively expressed on the surface of follicular lymphomas. Modest single-agent clinical activity was demonstrated in a Phase I study in relapsed or refractory, follicular NHL (ORR=11%). Preclinical data show that galiximab + rituximab may be more effective than either antibody alone. Here we report updated results from the Phase II part of a multicenter study (Study 114–21) evaluating galiximab + rituximab for relapsed or refractory, follicular NHL. Patients (pts) were administered galiximab (500 mg/m² qwk x 4) concurrently with a standard course of rituximab (375 mg/m² qwk x 4). Rituximab-refractory pts (no response or a response with TTP<6 months) were excluded. Study objectives were to evaluate safety, PK, and efficacy. Sixty-four pts received treatment. The median follow up is 14.5 months. Mean age at study entry was 59 yrs. The majority of pts (88%) were Stage III/IV, and FLIPI risk groups were distributed as good (27%), intermediate (39%), or poor (34%). All pts had received at least 1 prior lymphoma therapy; 42% were rituximab naïve. Galiximab infusions were delivered over 1 hr and were well tolerated. No DLTs were reported. Sixty-one (95%) pts experienced study-related AEs; the most common were lymphopenia (44%), leucopenia (38%), fatigue (38%), neutropenia (23%), and chills (23%). IWRC was used to evaluate response. An ORR of 64% was demonstrated: 17% CR, 14% CRu, and 33% PR. The median PFS was 12.1 months. Univariate analysis showed no correlation between response and baseline characteristics, although there was a trend for fewer responses in pts with elevated LDH, poor FLIPI score, and Grade III follicular histology. C_max and AUC values were dose-proportional, with a mean serum half-life of 13 to 24 days. These results were retrospectively compared with 3 historical Biogen Idec studies of follicular NHL pts treated with a standard course of rituximab monotherapy. Baseline characteristics were similar; however, there was a higher incidence of rituximab-naïve pts in the rituximab monotherapy group (77%) compared with galiximab + rituximab (42%). The toxicity profiles for the 2 groups were similar. The median PFS was longer in the galiximab + rituximab group (12.1 mo.) than in the historical rituximab monotherapy group (9.4 mo.). These results suggest that galiximab can be safely combined with a standard course of rituximab and produce promising response rates and PFS. The toxicity profile and PFS with this combination compared favorably with historical rituximab monotherapy studies. A Phase III, randomized study is planned.