'Tumor Monorail' Trial Aims to Derail Deadly Brain Cancer

DURHAM, NC – January 06, 2026 – In a significant development for neuro-oncology, the first patients have been enrolled in a pioneering clinical trial at Duke University's prestigious Preston Robert Tisch Brain Tumor Center. The study is evaluating a paradigm-shifting approach for treating recurrent glioblastoma, one of the most aggressive and lethal forms of brain cancer. At the heart of this trial is the "Tumor Monorail," an FDA-designated Breakthrough Device designed not only to treat the disease but to provide an unprecedented real-time window into the tumor's behavior.

Developed by clinical-stage company Exvade Bioscience, the Tumor Monorail is being tested in combination with a powerful dual-immunotherapy regimen. This multi-faceted strategy aims to overcome one of the most formidable challenges in cancer medicine: the inability to track a tumor's response and evolution over time without subjecting patients to repeated, high-risk brain surgeries. For patients with recurrent glioblastoma, a condition with no established standard of care, this trial represents a potential turning point in a long and arduous fight.

The 'Holy Grail' for a Devastating Disease

Glioblastoma (GBM) carries a grim prognosis. Even after initial treatment involving surgery, radiation, and chemotherapy, the cancer almost universally returns. For recurrent glioblastoma, the outlook is even more challenging, with median survival hovering around nine months and treatment options offering only modest benefits. A core reason for this difficulty lies within the brain itself; tumors are inaccessible, protected by the blood-brain barrier, and constantly evolving to resist treatment.

Historically, physicians have been forced to make treatment decisions based on periodic MRI scans, which provide limited information about the biological changes happening within the tumor. The only way to truly understand if a therapy is working at a cellular level, or how the tumor is developing resistance, has been through another invasive surgical biopsy. This limitation has been a major roadblock in developing more effective drugs.

"Serial tumor sampling remains one of the most critical unmet needs - and what many consider the holy grail - in glioblastoma therapeutic development and clinical advancement," said Nassir Mokarram, co-inventor of the Tumor Monorail and co-founder of Exvade Bioscience. The inability to get timely, actionable data from the tumor microenvironment has stymied countless clinical trials. "We believe effective treatments for many glioblastoma patients may already exist - but progress has been constrained by the lack of timely, accurate, and actionable insight into the tumor and its microenvironment," Mokarram added.

The Tumor Monorail is engineered to solve this very problem. It provides a permanent, safe conduit for researchers and clinicians to access living tumor cells throughout the entire course of treatment, potentially revolutionizing how new therapies are evaluated and personalized.

Engineering a New Path: How the Tumor Monorail Works

The Tumor Monorail is a masterclass in bio-inspired engineering. Instead of solely focusing on destroying cancer cells, it cleverly exploits their natural behavior. Glioblastoma cells are notoriously invasive, migrating along the brain's white matter tracts to spread and form new tumors. The Tumor Monorail device, a surgically implanted catheter system, mimics these pathways. It creates an artificial "track" that lures the migrating cancer cells, guiding them away from critical brain tissue and toward a subcutaneous collection port.

This ingenious design serves two primary functions. First, it potentially contains the tumor's spread, redirecting its invasive tendrils to a safe, manageable location. Preclinical studies in animal models were highly promising, showing the device could reduce tumor volume by over 90%. Second, and perhaps more importantly for clinical progress, the collection port allows physicians to repeatedly and minimally invasively sample living tumor cells in an outpatient setting, simply by using a needle to aspirate from the reservoir under the scalp.

This capability to perform "liquid biopsies" of the brain tumor itself is transformative. It unlocks the ability to conduct detailed molecular analysis over time, revealing how the tumor responds to treatment, when it begins to develop resistance, and what new targets might be emerging. In recognition of this potential, the U.S. Food and Drug Administration granted the Tumor Monorail its Breakthrough Device designation, a status reserved for technologies that could provide more effective treatment for life-threatening diseases and which helps expedite the regulatory review process.

A Dual-Pronged Attack: Integrating Device and Immunotherapy

The Phase 1 trial at Duke is not just a test of the device; it's a comprehensive therapeutic strategy that pairs the Monorail's monitoring capabilities with a potent, two-drug immunotherapy combination. This approach aims to deliver a one-two punch directly to the tumor.

The first agent, D2C7-IT, is an investigational immunotoxin. It is designed to bind to two proteins, EGFR and EGFRvIII, that are commonly overexpressed on the surface of glioblastoma cells. Once attached, it delivers a powerful toxin that kills the cancer cell. This initial attack is designed to break down the tumor and create an inflammatory response, effectively "priming" the area for the immune system.

The second agent, 2141-V11, is an anti-CD40 agonist antibody. Its job is to capitalize on the inflammation created by D2C7-IT by activating the body's own immune cells, particularly antigen-presenting cells, to mount a powerful and sustained attack against the cancer.

Both drugs are delivered directly into the tumor using a technique called convection-enhanced delivery (CED), which bypasses the formidable blood-brain barrier to ensure high concentrations of the therapy reach their target. While the initial dose is intracerebral, subsequent doses of the immune-boosting 2141-V11 are given subcutaneously in the neck to maintain a strong systemic response. At each of these follow-up doses, the Tumor Monorail's port is accessed, allowing the clinical team to evaluate the tumor's real-time status and see precisely how the combination therapy is performing.

World-Class Expertise at the Forefront

The trial is being conducted at a center with a storied history of tackling brain cancer. The Preston Robert Tisch Brain Tumor Center at Duke University has been a global leader in neuro-oncology research and patient care since 1937, pioneering novel immunotherapies, including its famous poliovirus therapy.

Leading the study is Dr. Annick Desjardins, a Professor of Neurosurgery and Neurology at Duke and a globally recognized expert in glioblastoma. Her work has been instrumental in advancing innovative treatments, and her expertise in techniques like CED is critical to the trial's success. She views the Tumor Monorail as a crucial tool for accelerating progress.

"By allowing real-time monitoring of the tumor over time, while on therapy, we will hopefully be able to more swiftly identify the degree of efficacy or the limitations of our therapies, while preventing the trauma and costs of repeated brain surgery," said Dr. Desjardins, the study's principal investigator.

This Phase 1 study, enrolling adults with recurrent glioblastoma who have exhausted standard therapies, represents more than just a test of a new device or new drugs. It is a test of a new philosophy in cancer treatment—one where real-time biological data can guide personalized therapeutic decisions, turning a static battle into a dynamic, adaptive strategy and offering a tangible glimmer of hope against one of medicine's most intractable foes.