Background: TG-0054 (burixafor) is a potent and selective antagonist of human chemokine receptor CXCR4 that inhibits the binding of stromal-derived factor 1 (SDF-1). Interruption of the CXCR4/SDF-1 interaction prevents sequestration of CD34+ stem cells to the bone marrow and subsequently mobilizes these cells into the peripheral blood within 1 to 3 hours of drug administration. Materials and Methods: An open-label, phase II pilot trial was conducted in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), or Hodgkin's lymphoma (HL) to evaluate the safety and stem cell mobilization of TG-0054 in combination with G-CSF. We planned to treat twelve patients with subcutaneous injections of 10 µg/kg/day G-CSF in the afternoon for 4 days. On the morning of Day 5, patients received 3.14 mg/kg TG-0054 and underwent large volume (18-24L) leukapheresis approximately 2 hours post-drug infusion. Patients were allowed by protocol to undergo leukapheresis for 1-5 days to obtain the predetermined target of ≥5.0 x 106 CD34+ cells/kg. 9 of 12 patients have been treated thus far with a plan to treat 3 additional patients. Results: A planned interim analysis revealed that6 of the 9 patients treated thus far collected more than 10 x 106 CD34+ cells/kg in 1 leukapheresis session. 2 patients required 2 days to achieve the study endpoint, and 1 outlier patient who had received Revlimid only 1 week prior to peripheral blood CD34 analysis failed to mobilize stem cells until he was allowed 2 more weeks to recover from his Revlimid treatment. Burixafor was well tolerated, and there were no adverse events that were attributed to the drug. All of the patients engrafted promptly after melphalan (7 patients) or BEAM (2 patients) conditioning regimens. Conclusion: Burixafor in combination with G-CSF is a potent and well-tolerated mobilizer of stem cells into the peripheral blood, and with the exception of 1 outlier, was able to mobilize >5.0 x 106 CD34+ cells/kg in 1-2 leukapheresis sessions in all patients treated thus far (median 1 day). This contrasts with our historical controls that required a median of 2-3 days to achieve a collection of ≥5.0 x 106 CD34+ cells/kg. A total of 12 patients will be treated on this pilot study. These encouraging results warrant the further testing of this drug in a larger randomized clinical trial. Disclosures Hsu: Taigen Biotechnology: Employment. Chang:Taigen Biotechnology: Employment. Schuster:Taigen Biotechnology: Research Funding.

Background TG-0054 (burixafor) is a potent and specific antagonist of the human CXCR4 chemokine receptor. TG-0054 blocks the interaction between CXCR4 and stromal cell-derived factor-1 (SDF-1), thus causing a rapid mobilization of stem cells from the bone marrow into peripheral blood within 1-3 hours of intravenous administration of the drug. Materials and Methods: An early phase II trial was conducted in patients with multiple myeloma (MM), non-Hodgkin lymphoma (NHL) or Hodgkin disease (HD) to evaluate the safety and stem cell mobilization of TG-0054 alone or in combination with G-CSF. 12 patients (1 HL, 7 MM, and 4 NHL patients) received an i.v. dose of 3.14 mg/kg TG-0054, and peripheral blood CD34 counts were assessed at 2, 4 and 6 hours post drug infusion. Patients who achieved at least 10 CD34 cell/ul in the peripheral blood were collected by large volume leukapheresis (24L) for 1-4 days to obtain a predetermined target of >2.5 x 106 CD34 cells /kg. Results: Seven patients (1 HD, 6 MM) were successfully mobilized with TG-0054 as a single agent achieving a cumulative CD34+ stem cell collection of 4.0 to 10.4 x106 cells /kg over 2-4 leukapheresis sessions. Patients who failed to mobilize with TG0054 as a single agent on day +1 were placed on the second arm of the study, where they received 5 doses of granulocyte colony stimulating factor (G-CSF) at a dose of 10 ug/kg beginning on day +4 with TG-0054added back in combination on day +8. These remaining five patients (1 MM, 4 NHL) who did not mobilize with TG0054 alone on day +1 and received G-CSF plus TG-0054 were leukapheresed on day +8. Those patients achieved a cumulative CD34 peripheral blood stem cell collection of of 3.2-21.0 x106 cells /kg over 1-4 leukaphereses sessions. Conclusion: TG-0054 exhibited potent and rapid mobilization of CD34+ stem cells, with favorable safety profile in patients. Engraftment All 12 patients received conditioning regimens (BEAM for the lymphoma patients and melphalan for the myeloma patients) followed by a stem cell infusion of at least 3.0 x106 CD34+ cells/kg. All patients engrafted without delay compared to historical controls. Median days to WBC engraftment were 12. Median days to platelet recovery of 20,000 and 50,000 were 20 and 20.5 days, respectively. Engraftment results of TG-0054 mobilized patients are similar to those seen in a matched group of historical controls. We have observed that mobilization with TG-0054 caused a preferential mobilization of mononuclear cells (MNC) component of the graft. Percent MNC in TG-0054 mobilized patients‘ grafts were 78.9+15.2 (median 81.5) as compared to percent of MNC in G-CSF mobilized patients‘ grafts of 62.6+27.7 (median 69.6). Disclosures: Schuster: TaiGen Biotechnology Co., Ltd: Research Funding. Tsai:TaiGen Biotechnology Co., Ltd: Employment. Hsu:TaiGen Biotechnology Co., Ltd: Employment, Equity Ownership. Chang:TaiGen Biotechnology Co., Ltd: Employment. Hsu:TaiGen Biotechnology Co., Ltd: Employment.