Researchers have dosed the first patient in the second part of a combined-phase clinical trial evaluating a combination of X4P-001 and Inlyta (axitinib) as a treatment for advanced kidney cancer.
The trial of X4 Pharmaceuticals‘ product is a Phase 1/2 study, with the Phase 2 part just starting.
“Efficiently progressing this study into Phase 2 is an important milestone for the development of X4P-001 and the CXCR4-targeted therapeutic approach,” Dr. Sudha Parasuraman, X4’s chief medical officer, said in a press release. “Having established the Phase 2 combination dose of X4P-001, we are now focused on augmenting proof of concept data for this critically important biological axis known to play a key role in immune cell trafficking.”
Scientists believe the CXCR4 receptor plays a role in 23 types of cancer, including a kidney cancer known as advanced clear cell renal cell carcinoma. X4P-001 inhibits the receptor, which binds the CXCL12 molecule.
CXCL12 recruits myeloid-derived suppressor cells and white blood cells called lymphocytes to tumors. Myeloid suppressor cells are a mix of immune cells that proliferate in the presence of cancer. Lymphocytes are also an immune system component.
Unfortunately, myeloid suppressor cells can participate in tumor growth through a variety of processes, including blockading tumor-killing T-cells and generating new tumor blood vessels.
Preclinical-trial studies have shown that X4P-001 can significantly reduce tumor growth and increase survival in animal models, either as a stand-alone therapy or in combination with approved therapies.
The randomized Phase 1/2 trial (NCT02667886) was designed to assess the safety and effectiveness of X4P-001, either alone or in combination with Inlyta, in patients with advanced renal cell carcinoma. Inlyta is a tyrosine kinase inhibitor approved for second-line treatment of patients with clear cell renal cell carcinoma. It is designed to prevent the formation of new tumor blood vessels.
The trial will be conducted in three parts. In Part A, patients will receive escalating daily doses of oral X4P-001 in combination with Inlyta. After determining the maximum dose of X4P-001 that patients can tolerate, researchers will give them either the maximum dose or half the maximum dose of X4P-001 in the Part B combo portion of the trial, and a stand-alone dose of X4P-001 in the Part C portion.
In the Phase 2 part of the trial, the main measures of X4P-001’s effectiveness will be objective response, which is either a complete or partial response to treatment; duration of response; and progression-free survival, or the time it takes for the disease to progress after treatment. The study will also look at the correlation between the therapy’s effectiveness and biomarkers of the disease.
X4 Pharmaceuticals will present results of the Phase 1 portion of the trial, including the dose selected for the Phase 2 component, at a medical meeting.
In addition to the Phase 1/2 trial, the company is exploring X4P-001 in combination with Opdivo (nivolumab) in a Phase 1/2 study of clear cell renal cell carcinoma patients (NCT02923531). And it’s looking at X4P-001 in combination with Keytruda (pembrolizumab) in a Phase 1b study of advanced melanoma patients (NCT02823405).