Rare Disease Report

New Combination Shows Promising Results in Clear Renal Cell Carcinoma

SEPTEMBER 11, 2017
Mathew Shanley
New clinical trial data presented at the European Society of Medical Oncology (ESMO) 2017 Congress in Madrid revealed that the combination of X4 Pharmaceuticals’ X4P-001-IO and Pfizer’s Inlyta (axitinib) demonstrated encouraging disease control rates and durable clinical responses in patients with clear cell renal cell carcinoma (ccRCC).

Results from the Phase 1 dose escalation are completed and enrollment in Phase 2 expansion is underway in the company’s ongoing Phase 1/2 study.
ccRCC is a form of kidney cancer that begins in the lining of the small tubes in the kidney. It is the most common variation of adult kidney cancer, and advanced ccRCC accounts for 20% of all diagnosis.

Currently, immunotherapies, kinase inhibitors and angiogenesis inhibitors are among popular therapies for the condition, however, there continues to be an unmet medical need with advanced ccRCC because stable responses continue to provide a clinical challenge for patients.

X4P-001-IO is an investigational selective, oral, small molecule inhibitor of C-X-X receptor 4 (CXCR4), which modulates immune function and angiogenesis through the trafficking of T-cells, dendritic cells, and myeloid-derived suppressor cells. Through CXCR4, it is hypothesized that X4P-001-IO can normalize the tumor microenvironment and improve endogenous anti-tumor responses.

Inlyta (axitinib) is a tyrosine kinase inhibitor approved in 2012 by the U.S. Food and Drug Administration (FDA) for second-line treatment of advanced renal cell carcinoma.

“The high disease control rate and clinical responses in previously treated patients with late-stage clear cell renal cell carcinoma underscore the rationale for investigating the therapeutic potential of CXCR4 inhibition plus VEGFR inhibition,” said Michael Atkins, MD, Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center in Washington, DC and William M. Scholl Professor of, Oncology at Georgetown University School of Medicine in a press release. “The preliminary results shown in this clinical study are very encouraging and support continued investigation of this approach.”

All 16 patients with advanced ccRCC in the Phase 1 study received at least 1 prior line of therapy and 69% of patients received at least 2. The combination of X4P-001-IO plus Inlyta was proven to improve disease control rate in 92% and objective response rate in 25%  of patients who completed the study (n=12).  The most frequent treatment-related adverse events (AEs) in patients included diarrhea, hypertension, fatigue, nausea, headache, decreased appetite, and vomiting.

“By leveraging data from prior clinical studies, we were able to quickly reach the recommended Phase 2 dose of X4P-001-IO, and the combination has demonstrated good tolerability with early signs of clinical activity,” said Sudha Parasuraman, MD, Chief Medical Officer of X4. “We look forward to presenting the full results of this study in 2018.”

The Phase 2 portion of the study continues to enroll patients to assess the efficacy of the drug via measures of objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS). A dose of 400 mg once daily for X4P-001-IO with 5 mg Inlyta twice daily has been selected for the study.

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