New Round Begins in Trial of X4P-001 and Opdivo as Treatment for Advanced Renal Cell Carcinoma

New Round Begins in Trial of X4P-001 and Opdivo as Treatment for Advanced Renal Cell Carcinoma

A combination of the investigational therapy X4P-001 and Opdivo (nivolumab) is being given to a patient with advanced clear cell renal cell carcinoma in a new round of a Phase 1 and 2 clinical trial, according to X4 Pharmaceuticals.

The company is continuing to enroll patients in this second round of the trial, which is being conducted in several U.S. cancer centers.

X4P-001 is an oral, small-molecule inhibitor of CXCR4, a receptor for the immune-stimulating protein CXCL12. Opdivo is an anti-PD-1 agent. PD-1 is a receptor that inhibits T-cells.

“Enabling the immune system to recognize and attack cancer cells is one of the most promising new approaches to improving outcomes for cancer patients,” Dr. David McDermott, the study investigator, said in a news release. He is an associate professor of Harvard Medical School and director of the Biologic Therapy Kidney Cancer Program at Beth Israel Deaconness Medical Center.

“While beneficial for some patients, single-agent immuno-therapy treatments have room for significant improvements in the durability and number of responses,” he said. “The evaluation of combination immuno-therapies is an important next step in cancer research. We are hopeful that X4P-001’s complementary mechanism of CXCR4 antagonism with PD-1 inhibition will demonstrate an innovative approach to modulating the immune system that yields improved patient outcomes.”

Studies have shown that the interaction of CXCR4 and CXCL12 in cancer modulates the migration of T-cells and immunosuppressive cells in the tumor. This impairs immune responses against the tumor cells and promotes the formation of new blood vessels.

By inhibiting this pathway, X4P-001 is expected to help immune cells track and destroy cancer.

Prior trials of X4P-001 in healthy volunteers and HIV-infected patients have shown it to be safe and well tolerated.

The Phase 1 and 2 trial (NCT02923531) is an open-label, single-arm, multicenter study evaluating the safety, tolerability and effectiveness of X4P-001 in combination with Opdivo in up to 20 patients who failed to respond to Opdivo alone.

The study’s primary focus is safety, which will be assessed by number of adverse side events. Other  measurements will include objective response rate, duration of response, patients’ disease-progression-free survival rate, and signs of biological activity in patients. An objective response is a complete or partial response to a treatment.

“Initiation of this study is an important milestone in our strategy to develop X4P-001 in ccRCC in combination with dual classes of existing approved drugs,” said Paula Ragan, PhD, president and CEO of X4. “Approved therapies address certain processes in the tumor microenvironment, but we believe more can be done to address the complex biology of challenging cancers, like ccRCC. By modulating cell trafficking in the microenvironment where cancer hijacks normal immune function, X4P-001 may be synergistic with other cancer therapies to result in enhanced responses.”

X4 is conducting two additional trials of X4P-001 in combination with approved therapies in cancer patients. A Phase 1 and 2 trial is assessing a combination of X4P-001 and Inlyta (axitinib) in patients with advanced ccRCC (NCT02667886). A Phase 1 trial is assessing X4P-001 in combination with Keytruda (pembrolizumab) in advanced melanoma patients (NCT02823405).