VX15 is an immunotherapy that Vaccinex is developing to treat solid tumors.

The company is also developing VX15 as a potential treatment for neurological disorders, including multiple sclerosis and Huntington’s disease.

How VX15 works

Semaphorin 4D, or SEMA4D, is a protein produced by immune cells, particularly T-cells. It interacts with a number of proteins in a range of processes. These include regulating the maturation, movement, and survival of cells in the immune system, nervous system, and blood-vessel system.

Some tumors produce high levels of SEMA4D. It activates the PLEXIN-B1 receptor, promoting tumor cell growth and the cancer’s migration to other tissue. High levels of SEMA4D in a tumor can prevent immune cells from entering the tumor site, reducing the body’s ability to fight cancer.

VX15 is an antibody that binds to SEMA4D, preventing it from interacting with its receptors. Blocking SEMA4D in tumor cells slows the cancer’s growth and prevents it from spreading to other tissue. VX15 also allows immune cells to enter the tumor to kill the cells there.

VX15 in clinical trials

Vaccinex has completed a Phase 1 clinical trial (NCT01313065) investigating VX15 in patients with advanced solid tumors. The company collaborated with PPD in the trial, which involved 42 patients at sites in Arizona and Texas.

Results, published in the medical journal Clinical Cancer Research, suggested that the treatment was safe and that patients tolerated it well. Common side effects included nausea, fatigue, joint pain, diminished appetite, fever, and reactions at the IV site where the drug was administered.

One patient experienced high levels of an enzyme called gamma-glutamyltransferase that is associated with liver damage. Researchers believed this was due to the cancer spreading to the liver before treatment with VX15.

A preliminary analysis of effectiveness suggested that VX15 had antitumor activity. Nineteen of  the 42 patients, or 45 percent, were able to achieve a stable disease for at least eight weeks. Eight patients, or 19 percent, had a stable disease for 16 weeks or more.

Patients with high levels of immune cells achieved longer progression-free survival before treatment,  suggesting that VX15 could benefit some patients more than others. Progression-free survival is the time it takes before a person’s cancer progresses.

Vaccinex is collaborating with Merck KGaA in a Phase 1/2 trial (NCT03268057) that is assessing a combination of VX15 and Merck’s avelumab as a treatment for non-small cell lung cancer, or NSCLC. The trial, called CLASSICAL-Lung, will be evaluating the combo’s safety and patients’ ability to tolerate it. About 40 patients with advanced NSCLC are expected to take part in the study at three U.S. sites.

The U.S. Food and Drug Administration has already approved avelumab under the name Bavencio to treat Merkel cell carcinoma and urothelial carcinoma. The therapy is an immune checkpoint inhibitor,  or substance that helps the immune system identify and target cancer cells.

The Phase 1/2 trial of VX15 for NSCLC will consist of dose escalation and dose expansion stages. One of the trial’s primary objectives will be to determine the maximum tolerated dose of VX15 when it’s used in combination with avelumab. Another objective will be to assess the combo’s safety and patients’ ability to tolerate it. In the dose expansion stage, researchers will make a preliminary assessment of the combo’s anti-tumor activity at the maximum tolerated dose researchers established in the first stage.

Meanwhile, the Children’s Oncology Group and National Cancer Institute is planning a Phase 1/2 clinical trial (NCT03320330) of VX15’s ability to counter young people’s advanced solid tumors. Patients will be from 1 to 30 years old and have solid tumors that failed to respond to other treatments or that returned.

Researchers plan to recruit 75 patients in California for the study’s Phase 1 stage.


Immuno-Oncology News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.