2549 Background: Small Modular Immuno-Pharmaceuticals (SMIPs) represent a novel proprietary biologic compound class that retain Fc mediated effector functions and are smaller than monoclonal antibodies. TRU-015, a SMIP that binds to CD20, depletes B cells in vitro and in animal models. TRU-015 has potent ADCC and apoptotic activity in vitro. By design, TRU-015 has attenuated CDC activity. We have evaluated the activity of TRU-015 in established human tumor xenograft models in nude mice. Methods: Nude mice were injected sub cutaneously with either Ramos or Daudi tumor cells. When large palpable tumors (> 200 mm3) were evident, mice (N ā„ 8/group) were treated with TRU-015 or comparator molecules. Groups were evaluated for median survival time (MST), tumor volume and percentage of tumor-free animals. Results: In nude mice bearing Ramos tumors >200mm3, TRU-015 treated mice demonstrated a significant enhancement in their median survival time (MST) in comparison to control mice (MST 44.5 d vs 11 d, p < 0.0001). In a more demanding model (tumor size > 370 mm3), TRU-015 treated mice also demonstrated a significant improvement in their MST in comparison to control mice (64.5 d vs 11 d, p < 0.0001). In nude mice bearing Daudi tumors, TRU-015 treated mice also showed a significant improvement in MST (40.5 d) in comparison to both rituximab (18 d, p<0.02) and control mice (10d, p<0.02). In addition, TRU-015 treated mice had decreased mean tumor volumes and a greater percentage of complete tumor regressions as compared to the other treatment groups in these tumor models. Conclusions: TRU-015 is effective in treating large, established tumors in these human tumor xenograft models. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Trubion Trubion