Subgroup exceeds target of 50% improvement in median progression-free survival, and 12% of patients remain on combination treatment with durations of 17 months or longer in X4 Pharmaceuticals’ Phase 2a portion of its open-label Phase 1/2 clinical trial of mavorixafor (X4P-001) in combination with axitinib (Inlyta®) in patients with advanced clear cell renal cell carcinoma (ccRCC). Data were presented at the European Society for Medical Oncology (ESMO) 2019 Congress today in Barcelona.
Combination therapy with mavorixafor and approved tyrosine kinase inhibitor (TKI) axitinib was generally well tolerated with a manageable safety profile and demonstrated clinical improvement with encouraging median progression free survival (mPFS) in a heavily pretreated advanced ccRCC patient population. Of the 65 patients in the trial, 49 patients (or 75%) received mavorixafor + axitinib as a third- to ninth-line therapy, having received between two and eight prior therapies with a TKI, immuno-oncology (IO) agent, or other systemic therapy. Fifty-seven of the 65 patients in the trial (or 88%) had an intermediate or poor prognosis.
This Phase 1/2, multi-center, open-label trial of mavorixafor in combination with axitinib included 65 patients with histologically confirmed advanced ccRCC, all of whom received at least one prior systemic therapy. Patients treated in the subgroup with immediate prior TKI therapy (n=34) demonstrated an objective response rate (ORR) of 18% and an increased mPFS of 7.4 months. This is a greater than 50% improvement from the 4.8-month historical mPFS with axitinib alone.1 Patients treated with mavorixafor + axitinib in the subgroup with immediate prior IO therapy (n=18) had an ORR of 61% and an increased mPFS of 11.6 months. In addition, eight of the 65 patients remain on the combination therapy today, with durations of treatment of 17 months or longer. Results suggest mavorixafor may enhance clinical response to axitinib and other TKIs that target tumor angiogenesis, as well as immunotherapy agents.
Mavorixafor is a potentially first-in-class, once-daily, oral, small molecule antagonist of chemokine receptor CXCR4. CXCR4 signaling is thought to contribute to the lack or loss of tumor responsiveness to angiogenesis inhibitors, like axitinib. Elevated expression of CXCR4 by RCC tumors is also correlated with an overall poor prognosis. In xenograft models studied previously, mavorixafor in combination with axitinib, a VEGF receptor TKI, reduced myeloid-derived suppressor cell infiltration and proangiogenic signals, and demonstrated greater than additive antitumor activity.
About X4 Pharmaceuticals
X4 Pharmaceuticals is developing novel therapeutics designed to improve immune cell trafficking to treat rare diseases, including primary immunodeficiencies and certain cancers. The company’s oral small molecule drug candidates antagonize the CXCR4 pathway, which plays a central role in immune surveillance. X4’s most advanced product candidate, mavorixafor (X4P-001), is in a global Phase 3 pivotal trial in patients with WHIM syndrome, a rare, inherited, primary immunodeficiency disease, and is currently also under investigation in combination with axitinib in the Phase 2a portion of an open-label Phase 1/2 clinical trial in clear cell renal cell carcinoma (ccRCC). X4 is also planning to commence clinical trials of mavorixafor in Severe Congenital Neutropenia (SCN) and Waldenström’s macroglobulinemia (WM) in 2019. The company was founded and is led by a team with extensive biopharmaceutical product development and commercialization expertise and is committed to advancing the development of innovative medicines on behalf of patients with limited treatment options. X4 is a global company that is headquartered in Cambridge, Massachusetts with research offices based in Vienna, Austria. For more information, please visit here.
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