Which clinical centres are participating in the GLIOMATCH prospective trials?
Five centres will participate in the GLIOMATCH prospective trials (see also clinical trials page). In addition to Leuven, the participating centres are Düsseldorf, Oslo, the Carlo Besta Institute in Milan and Erasmus MC in Rotterdam.
Together, these centres bring clinical expertise in the treatment of brain tumour patients and will contribute to the prospective part of the GLIOMATCH project. The trial network has also been expanded to support recruitment.
What is the design approach of the GLIOMATCH prospective trials?
The GLIOMATCH prospective trials will use a more or less common backbone. As Prof. De Vleeschouwer explains, they are designed as proof-of-concept studies that address detailed scientific questions on immuno-oncology therapies that have frequently been used for brain tumours in the past, combined with some novel approaches.
The trials will focus on targeted questions rather than immediately aiming to define a new treatment standard. Their purpose is to generate the deeper evidence needed to design larger future trials in immuno-oncology for brain tumours.
How are patient cohorts defined and harmonised across the trials?
The project will focus on cohorts of patients with glioblastoma that has recurred after initial standard-of-care treatment and who are eligible for reoperation. This makes it possible to harmonise the patient population across the different trials.
This approach also gives researchers access to tissue after standard-of-care therapy and, in some cases, after exposure to the novel approaches being investigated in the trial itself. These tissue samples are essential for understanding how the tumour and its immune environment respond to treatment.
What are the objectives and key immunotherapy strategies being investigated?
According to Prof. De Vleeschouwer, the overall aim is to contribute to the insights required to design larger future trials in immuno-oncology for brain tumours.
All trials have a proof-of-concept design. Four of them will work with some form of dendritic cell-based vaccination, a type of active specific immunotherapy. Some approaches will include an additional therapy that can be considered a form of adjuvant treatment.
Two centres will focus on checkpoint inhibition with PD-L1, a mechanism that has been identified as important in patients receiving vaccination. The group in Italy will investigate whether tetanus vaccination can help prime patients receiving dendritic cell vaccination and enhance the immunisation process.
In Leuven, a first-in-human trial will use a transnasally formulated and administered compound designed to target Galectin-1 in the tumour microenvironment. Galectin-1 is described as a key hub molecule that organises different types of immunosuppression. Finally, the colleagues in Rotterdam will focus on a new type of oncolytic virus therapy designed to trigger tumour immunity in a Phase 0/1 clinical trial.
How will these trials improve our understanding of patient response to immunotherapy?
The hope is that the project will provide deeper insights into what is needed to make patients susceptible to immunotherapy.
Prof. De Vleeschouwer explains that previous immunotherapy trials in brain tumours have shown that immune responses can be mounted in some patients. Those patients may benefit from therapy, but an important question remains: what makes the difference in susceptibility?
One likely factor is the immunosuppressive immune environment, which the project aims to modulate before triggering immunity through vaccination or other immunotherapy strategies. The combination of preparing the tumour environment and activating the immune system could help initiate a protective and tumour-rejecting immune response.
Ultimately, the prospective trials aim to generate enough evidence to inform larger future studies that may help set a new standard in immunotherapy for brain tumours.
Watch the video episode and discover the full GLIOMATCH: Explained series on our video page.
