On January 18, 2022 Global Coalition for Adaptive Research (GCAR) reported an update on the progress of GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment – NCT03970447) (Press release, , 18 18, 2022, View Source [SID1234605657]). GBM AGILE is a revolutionary patient-centered, adaptive platform trial for registration that tests multiple therapies for patients with newly-diagnosed and recurrent glioblastoma (GBM) – the deadliest form of brain cancer.

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Key updates

As of January 2022, GBM AGILE has screened over 1000 patients. Enrollment rates are 3 to 4 times greater than traditional GBM studies, with active sites averaging 0.75 to 1 patients/site/month.
With the active enrollment, Biohaven Pharmaceutical Holding Company Ltd.’s (NYSE: BHVN) troriluzole and Vigeo Therapeutics’ VT1021 have been selected to participate in GBM AGILE with anticipated commencement of recruitment in Q1 2022. They will be evaluated in all patient subgroups of the trial which include newly-diagnosed methylated MGMT, newly-diagnosed unmethylated MGMT, and recurrent GBM.
Biohaven’s troriluzole and Vigeo’s VT1021 will be the fourth and fifth arms to join the trial, respectively. GBM AGILE allows multiple drugs from different pharmaceutical companies to be evaluated simultaneously and/or over time against a common standard of care control.
GBM AGILE recently received IND approval in China for the evaluation of Kazia’s paxalisib. Study start up activities in China have commenced with site openings planned for Q2/Q3 2022.
GBM AGILE continues to expand its global access, with plans to open Europe including sites in Austria, France, Germany, Italy, and Switzerland in early 2022. Additional regions globally are being assessed.
GBM AGILE is an international, innovative platform trial designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization and a seamless phase 2/3 design. The trial, conceived by over 130 key opinion leaders, is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical partners to be evaluated simultaneously. With its innovative design and efficient operational infrastructure, data from GBM AGILE can be used as the foundation for a new drug application (NDA) and biologics license application (BLA) submissions and registrations to the FDA and other health authorities.

Biohaven’s troriluzole is a novel, orally administered small molecule that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. Troriluzole is thought to restore glutamate homeostasis by enhancing glutamate cycling, decreasing presynaptic glutamate release, and augmenting the expression and function of excitatory amino acid transporters (i.e., EAAT2) located on glial cells that play a key role in clearing excess glutamate from the synapse. Troriluzole was selected for inclusion in GBM AGILE, based on compelling evidence showing deregulation of glutamate in glioblastoma. The therapeutic potential of troriluzole in glioblastoma and other oncology indications is supported by several recent clinical and translational research studies conducted with troriluzole and its active moiety.

Dr. Michael Lim, Chair of the Department of Neurosurgery at Stanford University and Dr. Michael Weller, Director Department of Neurology, University Hospital Zurich, Switzerland have been selected to serve as arm Principal Investigators for troriluzole’s evaluation in GBM AGILE.

Vigeo’s VT1021, is a first-in-class dual modulating compound that blocks the CD47 immune checkpoint and activates the apoptotic and macrophage reprogramming activity of CD36. The result of the dual modulating activity is the induction of apoptosis in tumor and endothelial cells, as well as an increase in both CTL:Treg and M1:M2 macrophage ratio. The biological/therapeutic activity of VT1021 is mediated by the stimulation of thrombospondin-1 (Tsp-1). Through these dual-modulating effects VT1021 reprograms the tumor microenvironment from one that is immune suppressive, or "cold," to immune enhanced (or sensitized), or "hot," that are more susceptible to attack from the immune system. With its novel mechanism of action and clinical data from a Phase 2 expansion study in recurrent GBM patients, VT1021 is undergoing further studies to determine its effect in treating the disease, given that CD36 and CD47 are found to be highly expressed in tumor cells compared to normal brain tissue. Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors.

VT1021 will be led by arm Principal Investigators, Dr. Howard Colman, Professor, Huntsman Cancer Institute and Department of Neurosurgery, University of Utah, and Dr. Tom Mikkelsen, Medical Director, Henry Ford Precision Medicine Program & Clinical Trials.

The opening of study locations in Europe is anticipated to occur in early 2022 with sites planned in Austria, France, Germany, Italy, and Switzerland. Dr. Michael Weller, Director Department of Neurology, University Hospital Zurich, is serving as regional Principal Investigator of Europe.

"We are excited about the many achievements of GBM AGILE over the last 2.5 years since its launch," said Meredith Buxton, CEO, GCAR. "As an innovative collaboration between academic investigators, patient organizations and industry, GBM AGILE serves as a model for more efficient, cost-effective, and accelerated drug development. While we are encouraged by our accomplishments to date, we know have a lot more work to do to help identify and confirm new drugs for approval to support patients with GBM and their families. We are optimistic that GBM AGILE will provide important information to accelerate the evaluation of new treatments and may identify new and improved options for patients."