ERAS-801 for the Treatment of Resectable and Progressive or Recurrent IDH Wildtype Grade IV Glioblastoma or Astrocytoma With an EGFR Amplification or Mutation, ERAS801-SARG Trial

NCT07089641 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 24-5945NCI-2025-00605
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial tests the safety and side effects of ERAS-801 in treating patients with isocitrate dehydrogenase (IDH) wildtype, epidermal growth factor receptor (EGFR) amplified or mutated grade IV glioblastoma or astrocytoma that can be removed by surgery (resectable) and that is growing, spreading, or getting worse (progressive) or that has come back after a period of improvement (recurrent). Glioblastoma is the most common brain cancer in adults and survival rates remain poor despite treatment including surgery, radiation and chemotherapy. EGFR is a protein found on the surface of some cells, to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of tumor cells, so these cells may divide excessively in the presence of epidermal growth factor. ERAS-801, an EGFR inhibitor that can penetrate the central nervous system, binds to the tumor cells that express EGFR and may help shrink or slow the growth of the tumor cells.

Conditions

IDH Wildtype Glioblastoma; Recurrent Astrocytoma; IDH Wildtype Recurrent Glioblastoma; Resectable Astrocytoma; Resectable Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Adverse events will be described by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Will be presented using a 95% confidence interval and 2-sided p-value, combined with Bayesian posterior means and High Posterior Density intervals. Descriptive summaries and data visualization will be used

  From enrollment to 30 days after the last dose of study treatment

• Fludeoxyglucose F-18 (FDG) tumor uptake

  FDG positron emission tomography (PET), as measured by median normalized FDG standardized uptake value (SUV) within the contrast enhancing tumor, will be compared to estimate the change in FDG uptake in the tumor. A formal test for the mean difference will be based on a paired T-test. 95% confidence intervals will be used to quantify uncertainty in estimation

  Time Frame (Day 1 to Day 8 during pre-surgery treatment);at Baseline prior to Day 1 of pre-surgery study treatment & on Day 8 of Pre-surgery study treatment

Secondary Outcomes (3)

• Change in glycolytic index (GI)

  Time Frame ( Day 1 to Day 8 during pre-surgery treatment); at Baseline prior to Day 1 of pre-surgery study treatment & on Day 8 of Pre-surgery study treatment

• pH-weighted CEST-SAGE-EPI

  Time Frame ( Day 1 to Day 8 during pre-surgery treatment); at Baseline prior to Day 1 of pre-surgery study treatment & on Day 8 of Pre-surgery study treatment

• Level of ERAS-801

  Pre-surgery: Day 1, day 8, day 9; post-surgery: day 1 of each cycle (28 day cycle)

Study Arms (1)

Treatment (ERAS-801)

EXPERIMENTAL

Patients receive ERAS-801 PO QD for 8-14 days prior to undergoing scheduled surgical resection. Starting no more than 28 days after surgery, patients then receive ERAS-801 PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO, urine and blood sample collection and brain MRI throughout the study. Additionally, patients undergo CSF sample collection at the time of surgery and FDG PET on study.

Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Drug: EGFR Inhibitor ERAS-801; Other: Fludeoxyglucose F-18; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Surgical Procedure

Interventions

Biospecimen Collection PROCEDURE

Undergo urine, blood, and CSF sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (ERAS-801)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (ERAS-801)

EGFR Inhibitor ERAS-801 DRUG

Given PO

Also known as: ERAS 801, ERAS-801, ERAS801

Treatment (ERAS-801)

Fludeoxyglucose F-18 OTHER

Given FDG

Also known as: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Treatment (ERAS-801)

Magnetic Resonance Imaging PROCEDURE

Undergo brain MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (ERAS-801)

Positron Emission Tomography PROCEDURE

Undergo FDG PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (ERAS-801)

Surgical Procedure PROCEDURE

Undergo surgical resection

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (ERAS-801)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be 18 years of age or older on the day of signing informed consent
• Patients must have histologically proven surgically accessible World Health Organization (WHO) grade IV glioblastoma/astrocytoma, which is progressive or recurrent following radiation therapy +/- chemotherapy
• Patient tumor sample must have wild type IDH with evidence of EGFR mutation/amplification by Clinical Laboratory Improvement Act (CLIA)-certified laboratory assay
• Patients may have had no more than two prior recurrences
• Patient must be able to tolerate MRIs. Pre-study enrollment MRIs must be available for central review, including at least the immediate pre-progression scan and the scan demonstrating progression. Patients must have measurable, by RANO, supratentorial contrast-enhancing progressive or recurrent high-grade glioma by MRI imaging within 7 days of starting treatment
• Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy
• weeks from a non-nitrosourea chemotherapy
• weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
• weeks from the last treatment with bevacizumab
• weeks from administration of a non-cytotoxic, FDA-approved agent other than bevacizumab (e.g., hydroxychloroquine, etc.)
• week from the tumor treating fields
• Patients must be undergoing surgery that is clinically indicated as determined by their care providers. Patients must be eligible for surgical resection according to the following criteria:
• Expectation that the surgeon can resect at least 500 mg of tumor from enhancing tumor and 100 mg from non-enhancing tumor with low risk of inducing neurological injury

You may not qualify if:

• Participants may not be receiving any other investigational agents
• Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ERAS-801 are ineligible
• Participants with prior therapy with EGFR inhibitors are ineligible because treatment with EGFR kinase inhibitors or other EGFR-targeted agents has the potential to deplete the tumor of EGFR-amplified or EGFR mutant cell populations and confound the evaluation of ERAS-801 effects on participants
• Participants on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol. Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of ERAS-801
• Participants must not have evidence of significant hematologic, renal, or hepatic dysfunction
• Participants must not have evidence of significant intracranial hemorrhage
• Participants with clinically significant cardiovascular disease including, but not limited to:
• Myocardial infarction or unstable angina within the 6 months prior to the first dose of study drug
• Clinically significant cardiac arrhythmia
• Prolonged QTcF \> 450 ms
• Uncontrolled (persistent) hypertension: systolic blood pressure \> 180 mmHg; diastolic blood pressure \> 100 mmHg
• Congestive heart failure (New York Heart Association class III-IV)
• Use of pacemaker
• Pulmonary embolism \< 30 days
• Participants with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

RECRUITING

MeSH Terms

Conditions

Astrocytoma

Interventions

Specimen Handling; Fluorodeoxyglucose F18; Magnetic Resonance Spectroscopy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Deoxyglucose; Deoxy Sugars; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Phioanh Nghiemphu, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Quan Li

CONTACT

310-825-1416; QuanLi@mednet.ucla.edu

Emese Filka

CONTACT

310-825-1416; EFilka@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2025
• First Posted: July 28, 2025
• Study Start: July 28, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-07

Locations

US (1)