* Safety and Immune Response to FMPV-1 (QSC204718)
Research type
Research Study
Full title
A Phase I Study of FMPV-1 in Healthy Male Subjects to Assess Safety and Immune Response
IRAS ID
304937
Contact name
Dr Sarah Arbe-Barnes
Contact email
Sponsor organisation
Hubro Therapeutics AS
Eudract number
2020-004363-80
Duration of Study in the UK
1 years, 3 months, 18 days
Research summary
Research Summary:
The Sponsor is developing the test medicine in the form of a vaccine, FMPV-1, for the potential treatment of certain types of cancer, for example colon cancer and stomach cancer. These cancers are commonly linked to a molecular problem called Microsatellite Instability (MSI).MSI causes DNA to mutate so it is less effective at repairing itself. A build up of this mutated DNA can then lead to diseases such as cancer. As many types of cancer caused by MSI have similar mutated proteins, parts of these proteins can be used to make a vaccine to train the immune system to fight these cells.
The study will try to assess how the body’s immune system responds to the test medicine, as well as the safety and tolerability of the test medicine.
This will be the first time the test medicine is given to humans.
This is a single-part, open-label, non-randomised study involving up to 16 healthy male volunteers, ages 18 - 55. There will be two sequential groups of volunteers and both groups will receive the test medicine on 5 occasions over a 6-week time period as an injection into the upper arm. Volunteers will also return to the clinic on 5 separate occasions as out-patients for blood samples and safety assessments to be performed.
Volunteers will be required to return to the clinic on 2 further occasions for follow-up visits at 6 months and 12 months post-first dose.
Lay summary of study results: Colorectal cancer is the second most common in women and third most common cancer in men worldwide corresponding to an estimated 8.3% of cancer-related deaths annually. A proportion of colorectal cancer patients have a type called microsatellite instability (MSI) high (MSI-H) caused by a deficiency in genetic repair, which means that normal cells are not able to repair themselves properly leading to the cancer formation. In these patients a specific type of treatment is needed. MSI-H features occur in different cancers including an inherited tendency to develop cancer called Lynch Syndrome.
The cancer-specific vaccine FMPV-1 is designed to activate the immune system specifically against MSI-H cancers which have a further genetic deficiency called a frameshift mutation. FMPV-1 is administered in combination with an agent which boosts the immune response known as an adjuvant (GM-CSF) and is being developed for the treatment of MSI-H cancers. These are injected into the skin on a regular basis.
This first clinical study with FMPV-1 and GM-CSF was conducted in 16 healthy male volunteers to assess the safety and immunogenicity (ability to generate an immune response) of the potential cancer vaccine. This was considered to be the best initial approach to assess the safety of the vaccination and to examine the immune response of FMPV-1 and GM-CSF. The subjects received 5 injections into the skin at intervals over a period of 6 weeks. They had tests to look at the safety of the vaccination as the immune response (both as skin reactions suggesting that the immune response has occurred and the production of specific T-cells. T-cells are lymphocytes) that are important in cancer killing for tumours that are MSI-H and also have the frameshift mutation. The subjects were followed up for 12 months to see how long their immunity was lasting.
The vaccine was considered to be well tolerated by all subjects, with only mild skin-type reactions seen in 6 subjects regarded as being due to the vaccine itself. The immune response was tested using a skin reactivity test which was recorded at time intervals which coincided with the vaccination schedule. The skin reactivity test showed responses occurred in 94% (15/16) of subjects within 6 weeks and in half of them after 4 weeks. This indicates that FMPV-1 was able to generate specific immune responses during the vaccination period and that there was evidence of immune memory after 6 months following the first vaccination. There was also evidence that FMPV-1 specific T-cell generation occurred in some of the subjects suggesting that these would also be produced in patients who had MSI-H and frameshift mutation cancers.
The safety and immune response data from this study support the assessment of the immunological response in cancer patients in future research.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
21/FT/0147
Date of REC Opinion
27 Oct 2021
REC opinion
Further Information Favourable Opinion