2961 - Safety and pharmacokinetics of novel CXCR4 antagonist YF-H-2015005 in the mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma

Background

YF-H-2015005, a new type of CXCR4 antagonist, has demonstrated an ability to mobilize CD34+ cells in peripheral blood in pre-clinical studies. In this study, we evaluated the safety and efficacy of YF-H-2015005, as well as its pharmacokinetic (PK) and pharmacodynamic (PD) characteristics when administered with granulocyte colony-stimulating factor (G-CSF) in patients with non-Hodgkin lymphoma (NHL).

Methods

This phase I, open-label, single arm study enrolled patients who had HNL, aged 18 to 65 years, and eligible for autologous stem cell transplantation. The stem cell mobilization regimen used was G-CSF (10 mg/kg/day subcutaneously) administration in the morning for up to 8 days, and YF-H-2015005 (0.24 mg/kg subcutaneously) initialed in the evening of the fourth day of G-CSF administration, and then continued for up to 4 days. Apheresis was initiated 9 to 10 hours after each evening dose of YF-H-2015005, and after the morning dose of G-CSF. Apheresis was repeated for up to 4 days or until ≥ 2 × 10⁶ CD34+ cells/kg had been collected.

Results

A total of 15 patients (11 men and 4 women; median age 51 years, range 32-64 years) were enrolled in the study. Our PK data showed that YF-H-2015005 was rapidly absorbed after s.c. administration with a median T_max of 0.5 hour, and then was rapidly cleared with a terminal half-life of 5.04 ± 1.00 hours. After the first dose of YF-H-2015005, a mean 2.0-fold to 2.9-fold increase in peripheral blood CD34+ cells from baseline was observed after 2 to 24 hours, with the maximum increase being observed at 10 hours after dosing. Fourteen (93%) patients reached the minimum target CD34+ cell collection of ≥ 2 × 10⁶ cells/kg required for transplantation. No adverse event ≥ grade 3 or treatment-related serious adverse event occurred.

Conclusions

YF-H-2015005 was safe and effective when used to mobilize CD34+ cells for transplantation in patients with NHL.

Clinical trial identification

CTR20170925.

Editorial acknowledgement

Legal entity responsible for the study

Hefei Yifan Biopharmaceuticals Inc.

Funding

Hefei Yifan Biopharmaceuticals Inc.

Disclosure

All authors have declared no conflicts of interest.