GBM AGILE: Eligibility, Sites, and the Paxalisib Update

The GBM AGILE trial — and why most patients haven't heard of it

When someone is first diagnosed with glioblastoma (GBM), the treatment conversation often sounds the same: surgery, radiation, and temozolomide chemotherapy. That combination has been the standard of care for nearly two decades.

GBM AGILE is working to change that. Rather than testing one drug in one patient population, it tests multiple therapies at the same time — adjusting the trial in real time based on what the data shows. It's currently enrolling at more than 60 sites across the US and internationally, and one of its therapies may be closer to FDA approval than most people realize.

What makes GBM AGILE different from a standard clinical trial

GBM AGILE is an adaptive platform trial — a single master protocol that evaluates multiple drugs simultaneously across both newly diagnosed and recurrent GBM patients. Most clinical trials test one drug; GBM AGILE tests several at once and continuously updates how patients are assigned based on incoming results.

The key mechanism is Bayesian response adaptive randomization. In plain terms: the trial analyzes data continuously and shifts enrollment toward arms that are performing better. Arms showing stronger signals get more patients. Arms that aren't performing get wound down. New therapies can be added as the trial progresses.

This design compresses the timeline significantly. Meaningful data on multiple treatments can emerge in a fraction of the time a conventional series of trials would require.

Who is eligible for GBM AGILE

GBM AGILE enrolls two distinct patient populations:

Newly diagnosed GBM: Patients must have histologically confirmed Grade IV GBM (IDH wild-type), have undergone surgical resection or biopsy, and have a Karnofsky Performance Status — a measure of functional ability — of 60 or higher. Tumor tissue must be available for molecular profiling.

Recurrent GBM: Patients at first or second recurrence following initial treatment that included radiation therapy. Karnofsky Performance Status of 70 or higher is required. Prior treatment with bevacizumab or other anti-VEGF agents is an exclusion.

MGMT methylation status — a chemical modification of a DNA repair gene that affects how tumors respond to chemotherapy — is used as a stratification factor, meaning patients are grouped by their MGMT status when assigned to treatment arms.

What therapies are being tested

GBM AGILE has evaluated multiple agents including temozolomide, lomustine, regorafenib, and paxalisib. Arms can be added or removed as data accumulates.

Paxalisib is among the most closely watched agents currently in the trial. It's an inhibitor of the PI3K/mTOR pathway — a signaling pathway frequently activated in GBM — that is specifically engineered to cross the blood-brain barrier, which most drugs cannot do. That blood-brain barrier problem is one of the core reasons so many GBM treatments fail: even drugs that work in lab settings often can't reach the tumor.

The FDA signal on paxalisib in 2026

The FDA has communicated that overall survival data generated by paxalisib within GBM AGILE may be sufficient to support a standard approval pathway. The agency has aligned with the trial's developers on the design of a pivotal Phase 3 study — including the patient population, primary endpoint, and comparator arm.

Standard FDA approval for a GBM therapy would be the first of its kind in many years. The field has seen accelerated approvals later withdrawn, and bevacizumab received full approval, but the GBM pipeline has historically been marked by late-stage failures. Nothing is approved yet. The data will need to meet pre-specified thresholds, and a confirmatory study is part of the path forward. But the directional signal from the agency is notable.

Where GBM AGILE is running

GBM AGILE is currently enrolling at more than 60 sites across the United States, Australia, Canada, and Europe. US participating institutions include:

• Massachusetts General Hospital and Dana-Farber Cancer Institute (Boston)
• Memorial Sloan Kettering Cancer Center (New York)
• MD Anderson Cancer Center (Houston)
• University of California, San Francisco
• Cedars-Sinai Medical Center (Los Angeles)
• Yale Cancer Center (New Haven)
• Duke University Medical Center (Durham)
• University of Pennsylvania (Philadelphia)
• Ohio State University Comprehensive Cancer Center (Columbus)

A full list of active sites is available at ClinicalTrials.gov (NCT03970447).

What This Means for Patients

GBM AGILE matters for patients for two reasons. First, it offers access to experimental therapies — including paxalisib — not available outside of a clinical trial. Second, the breadth of its site network means geographic access is less of a barrier than with many smaller studies.

For patients who have been told there are limited next steps, this trial represents a structured, scientifically rigorous path to additional options — at institutions with dedicated neuro-oncology expertise.

If you're newly diagnosed or approaching a recurrence, asking your oncologist specifically about GBM AGILE eligibility is worth the conversation.

How to take action

The trial record for GBM AGILE is at clinicaltrials.gov/study/NCT03970447. It includes the full eligibility criteria, contact information for each site, and current enrollment status.

PACT AI can help you review your diagnosis, identify which GBM AGILE arms may be relevant to your situation, and find other trials that match your profile. Visit pact-ai.com to get started.

Have questions? Reach out at contact@pact-ai.com.

Frequently asked questions

Is GBM AGILE still enrolling patients in 2026?

Yes. GBM AGILE (NCT03970447) is actively enrolling patients at more than 60 sites globally, including major US cancer centers. Contact the trial site nearest you through ClinicalTrials.gov for current enrollment status by arm.

Who is not eligible for GBM AGILE?

Patients with prior bevacizumab or anti-VEGF treatment are excluded from the recurrent GBM arm. Newly diagnosed patients must have histologically confirmed IDH wild-type Grade IV GBM and a Karnofsky Performance Status of at least 60.

How is GBM AGILE different from a standard Phase 3 trial?

A standard trial tests one drug with fixed patient assignments. GBM AGILE tests multiple therapies simultaneously and uses adaptive randomization — shifting more patients toward arms showing better results as data accumulates. This accelerates meaningful findings across several treatments at once.

Can I enroll if I'm being treated outside the US?

Yes. GBM AGILE sites operate in Australia, Canada, and Europe in addition to the United States. The full list of international sites is available at ClinicalTrials.gov under NCT03970447.

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This post is for informational purposes only and does not constitute medical advice. Clinical trial eligibility is determined by the treating physician and trial investigators based on each patient's individual medical history.