X4P-001 is an orally bioavailable CXCR4 antagonist that has demonstrated activity in various tumor models. CXCR4 (C-X-C chemokine receptor type 4) is the receptor for CXCL12 (C-X-C chemokine ligand type 12). CXCL12 has potent chemotactic activity for lymphocytes and MDSCs (myeloid-derived suppressor cells), and is important in homing of hematopoietic stem cells to the bone marrow. CXCR4 is also expressed and active on multiple types of human cancers, including ccRCC, ovarian cancer, and melanoma, and increased expression of CXCR4 on tumor cells has been associated with significantly decreased overall patient survival.~Multiple observations implicate the CXCL12/CXCR4 axis in contributing to the lack (or loss) of tumor responsiveness to angiogenesis inhibitors (also referred to as angiogenic escape). In animal cancer models, interference with CXCR4 function has been demonstrated to disrupt the tumor microenvironment and unmask the tumor to immune attack by multiple mechanisms, including:~Eliminating tumor re-vascularization~Decreasing the infiltration of MDSCs~Increasing the ratio of CD8+ T cells to Treg cells~The hypothesis is that effective CXCR4 antagonism by X4P-001 would be of potential benefit in patients with advanced ccRCC and other cancers by multiple mechanisms:~Decreased recruitment of MDSCs, resulting in increased anti-tumor immune attack~Sustained decrease in neoangiogenesis and tumor vascular supply~Interference with the autocrine effect of increased expression by ccRCC of both CXCR4 and CXCL12, its only ligand, thereby, potentially reducing cancer cell metastasis~This initial clinical trial in patients with advanced ccRCC will evaluate X4P-001 both as a single agent (monotherapy) and also in combination with axitinib, a small molecule TKI (tyrosine kinase inhibitor) approved for second-line treatment of patients with ccRCC. This combination has the potential to further improve outcomes by reducing the angiogenic escape that typically occurs with TKI therapy.
The purpose of the study is to test different doses of X4P-001 given alone and in combination with axitinib in patients diagnosed with advanced renal cell carcinoma. The goals of the study are to determine the safety and tolerability of X4P-001, as well as the potential effect it may have on the body and the cancer tumor.