GSK and VBI Vaccines Announces Phase 2a Evaluation of Vaccine Candidate For Recurrent Glioblastoma

VBI Vaccines, Inc. announced a collaboration with GlaxoSmithKline (GSK) to clinically evaluate the combination of the cancer vaccine immunotherapeutic VBI-1901, with GSK’s proprietary AS01(B) adjuvant system.

As part of the collaboration, VBI said on September 10, 2019, ‘it plans to add an additional study arm to Part B of the company’s ongoing, multi-center, open-label Phase 1/2a clinical study targeting recurrent glioblastoma (GBM), a cytomegalovirus (CMV)-associated tumor.’

This is important research since GBM accounts for about 17 percent of all tumors of the brain. 

In Part A of the study, VBI-1901 adjuvanted with granulocyte-macrophage colony-stimulating factor (GM-CSF) was well-tolerated at all doses. Further, 3 out of 6 patients in the high-dose (10 µg) cohort demonstrated evidence of stable disease by magnetic resonance imaging (MRI), which correlated with vaccine-induced immune response. 

Based on this safety and immunogenicity data, the high-dose was identified as the optimal therapeutic dose to test in the Part B extension phase of the study.

Part B of the ongoing Phase 1/2a clinical study is now planned to be a 2-arm, open-label study, enrolling 20 first-recurrent GBM patients to receive VBI-1901 in combination with either GM-CSF or AS01B as immunomodulatory adjuvants.

The enrollment of the 10 patients in the VBI-1901 with GM-CSF arm was initiated at the end of July 2019. 

The initiation of enrollment of the 10 patients in the VBI-1901 with AS01B arm is expected later in the second half of 2019, subject to U.S. Food and Drug Administration (FDA) acceptance of the amended protocol.

“VBI-1901 has shown encouraging results in Part A of the ongoing Phase 1/2a clinical study in recurrent GBM patients and we are excited to be able to expand the scope of Part B to assess the candidate in combination with AS01B, a highly-innovative adjuvant system that has contributed to positive results in combination with the gE antigen in GSK’s shingles vaccine, Shingrix,” said David E. Anderson, Ph.D., VBI’s Chief Scientific Officer.

“VBI’s enveloped virus-like particle (eVLP) technology, the basis for VBI-1901, is highly versatile and has demonstrated clinical potency in both preventative and therapeutic settings.” 

“We believe that these two technologies may be an ideal match for next-generation vaccines, and we look forward to seeing the results of this collaboration,” said Dr. Anderson in a press release.

Glioblastoma multiforme is a fast-growing glioma that develops from star-shaped glial cells that support the health of the nerve cells within the brain.

GBM is often referred to as a grade IV astrocytoma. 

These are the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue.

The National Cancer Institute estimates that 22,850 adults were diagnosed with brain and other nervous system cancer in 2015. GBM has an incidence of two to three per 100,000 adults per year and accounts for 52 percent of all primary brain tumors.

And, during June 2019, the US Centers for Disease Control and Prevention (CDC) updated its  Cytomegalovirus information to say ‘CMV is a common virus for people of all ages; however, a healthy person’s immune system usually keeps the virus from causing illness.’

In the United States, nearly 1 in 3 children are already infected with CMV by age five. Babies born with CMV can have brain, liver, spleen, lung, and growth problems. 

Diagnostic tests of saliva or urine are preferred to detect CMV in newborns.

The most common long-term health problem in babies born with congenital CMV infection is hearing loss, which may be detected soon after birth or may develop later in childhood.

For babies with signs of congenital CMV infection at birth, antiviral medications, primarily valganciclovir, may improve hearing and developmental outcomes. Valganciclovir can have serious side effects and has only been studied in babies with signs of congenital CMV infection. 

There is limited information on the effectiveness of valganciclovir to treat infants with hearing loss alone, says the CDC.

Moreover, over half of adults by age 40 have been infected with CMV. Healthy people who are infected with CMV usually do not require medical treatment.

Once CMV is in a person’s body, it stays there for life and can reactivate. 

A person can also be re-infected with a different strain of the virus. Most people with CMV infection have no symptoms and aren’t aware that they have been infected.

CMV Signs and Symptoms

• In some cases, infection in healthy people can cause mild illness that may include Fever, Sore throat, Fatigue, and Swollen glands.
• Occasionally, CMV can cause Epstein-Barr Virus or hepatitis.
• People with weakened immune systems who get CMV can have more serious symptoms affecting the eyes, lungs, liver, esophagus, stomach, and intestines.

CMV Transmission

• People with CMV may pass the virus in body fluids, such as saliva, urine, blood, tears, semen, and breast milk. CMV is spread from an infected person in the following ways:
  • From direct contact with saliva or urine, especially from babies and young children
  • Through sexual contact
  • From breast milk to nursing infants
  • Through transplanted organs and blood transfusions

CMV Diagnosis and Treatment

• Blood tests can be used to diagnose CMV infection in adults who have symptoms. However, blood is not the best fluid to test newborns with suspected CMV infection. 
• Medications are available to treat CMV infection in people who have weakened immune systems and babies with signs of congenital CMV, said the CDC.

VBI’s ongoing 2-part study is being conducted at the Neurological Institute of New York Columbia University Medical Center, Dana-Farber Cancer Institute, and Massachusetts General Hospital.

Published by Vax Before Cancer