ERAS-801 for the Treatment of Resectable and Progressive or Recurrent or Elderly Newly Diagnosed IDH Wildtype Grade IV Glioblastoma or Gliosarcoma With an EGFR Amplification or Mutation, ERAS801-SARG Trial
A Phase Ib Open Label Clinical Trial to Evaluate the Safety and Efficacy of ERAS-801 in Recurrent Glioblastoma or Elderly Newly Diagnosed Glioblastoma Patients With EGFR Amplification and/or Mutation (ERAS-801-3.0)
3 other identifiers
interventional
50
1 country
2
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 gliosarcoma that can be removed by surgery (resectable) and that is growing, spreading, or getting worse (progressive), that has come back after a period of improvement (recurrent) or that is newly diagnosed in an elderly patient. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2025
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 10, 2025
CompletedFirst Posted
Study publicly available on registry
July 28, 2025
CompletedStudy Start
First participant enrolled
July 28, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 30, 2028
July 20, 2026
June 1, 2026
2 years
April 10, 2025
July 16, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Fludeoxyglucose F-18 (FDG) tumor uptake (Cohort A)
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. Analyses will be descriptive, summarizing changes with confidence intervals and exploring correlations; no formal hypothesis testing is planned.
At baseline, prior to initiation of study treatment and after study treatment prior to surgery
Pharmacokinetics (PK) dose modification (Cohort B)
Will evaluate the effect of 120 mg twice daily dosing on corrected QT interval (QTc) relative to maximum concentration compared with historical 240 mg once-daily data. PK data and triplicate electrocardiograms will be summarized descriptively, with QTc analyzed as a continuous change.
At day 1 and day 15
6 month progression free survival (Cohort C)
Will be summarized as a proportion with corresponding 95% exact confidence intervals. Nominal exact two-sided p-values will be presented, testing EGFR inhibitor ERAS-801 against a fixed 5% null rate. Simon's minimax two-stage design will be used for conducting the trial.
At 6 months
Secondary Outcomes (4)
Incidence of adverse events
From enrollment to 30 days after the last dose of study treatment
Change in glycolytic index (GI)
At baseline, prior to initiation of study treatment and after study treatment prior to surgery
pH-weighted CEST-SAGE-EPI
At baseline, prior to initiation of study treatment and after study treatment prior to surgery
PK profile
At time of surgery and then at the beginning of each treatment cycle (1 cycle = 28 days)
Study Arms (3)
Cohort A (ERAS-801)
EXPERIMENTALPatients 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.
Cohort B (ERAS-801)
EXPERIMENTALAfter first or second recurrence, patients receive ERAS-801 PO BID 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 and FDG-PET throughout the study.
Cohort C (ERAS-801)
EXPERIMENTALWithin 2-4 weeks of the last tumor surgery, newly diagnosed patients receive ERAS-801 PO BID 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 and FDG-PET throughout the study.
Interventions
Undergo ECHO
Given FDG
Undergo FDG PET
Undergo surgical resection
Given PO
Undergo brain MRI
Undergo urine, blood, and CSF sample collection
Eligibility Criteria
You may qualify if:
- COHORT A: Patients must be 18 years of age or older on the day of signing informed consent
- COHORT A: Patients must have histologically proven surgically accessible World Health Organization (WHO) grade IV glioblastoma/gliosarcoma, which is progressive or recurrent following radiation therapy +/- chemotherapy
- COHORT A: Patient tumor sample must have wild type IDH with evidence of EGFR mutation/amplification by Clinical Laboratory Improvement Act (CLIA)-certified laboratory assay. Patients with EGFR mutations in T790M or exon 20 will be excluded
- COHORT A: Patients may have had no more than two prior recurrences
- COHORT A: 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 28 days prior to enrollment
- COHORT A: 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
- COHORT A: 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 (if available) with low risk of inducing neurological injury
- +70 more criteria
You may not qualify if:
- COHORT A: Participants may not be receiving any other investigational agents
- COHORT A: Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ERAS-801 are ineligible
- COHORT A: Participants with prior therapy with EGFR inhibitors such as EGFR kinase inhibitors or other EGFR-targeted agents that have the potential to deplete the tumor of EGFR-amplified or EGFR mutant cell populations and confound the evaluation of ERAS-801 effects on participants are ineligible. If a participant had received previous treatment with EGFR-targeted agents but tumor resection after completing this treatment still shows EGFR amplification, patient might still be eligible and should be discussed with the principal investigator (PI)
- COHORT A: 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
- COHORT A: Participants must not have evidence of significant hematologic, renal, or hepatic dysfunction
- COHORT A: Participants must not have evidence of significant intracranial hemorrhage
- COHORT A: 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
- COHORT A: 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
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Phioanh Nghiemphu
UCLA / Jonsson Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- 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
July 20, 2026
Record last verified: 2026-06