Recruiting
Phase 1

ERAS-801

Sponsor:

Jonsson Comprehensive Cancer Center

Code:

NCT07089641

Conditions

Glioblastoma

Glioblastoma, IDH-Wildtype

Gliosarcoma

Recurrent Glioblastoma, IDH-Wildtype

Recurrent Gliosarcoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Echocardiography Test

EGFR Inhibitor ERAS-801

Fludeoxyglucose F-18

Magnetic Resonance Imaging

Study Details

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.

Conditions

Glioblastoma

Glioblastoma, IDH-Wildtype

Gliosarcoma

Recurrent Glioblastoma, IDH-Wildtype

Recurrent Gliosarcoma

Study ID

NCT07089641

Start date

Jul 28, 2025

Status verified date

Jun, 2026

Completion date

Jul 30, 2028

Anticipated

Primary completion date

Jul 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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:

  • 12 weeks from the completion of radiation
  • 6 weeks from a nitrosourea chemotherapy
  • 3 weeks from a non-nitrosourea chemotherapy
  • 4 weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
  • 4 weeks from the last treatment with bevacizumab
  • 2 weeks from administration of a non-cytotoxic, FDA-approved agent other than bevacizumab (e.g., hydroxychloroquine, etc.)
  • 1 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
  • COHORT A: Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment). The following amount of tissue is requested: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 30 FFPE unstained slides (5µm thick)
  • COHORT A: Patients must have a Karnofsky performance status ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • COHORT A: Absolute neutrophil count (ANC) ≥ 1000/uL
  • COHORT A: Platelets ≥ 100,000/uL
  • COHORT A: Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L

  • Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
  • COHORT A: Creatinine ≤ 1 x upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥ 30 mL/min for participant with creatinine levels > 1 x institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\])

  • Creatinine clearance (CrCl) should be calculated per institutional standard
  • COHORT A: Total bilirubin ≤ 1.5 x ULN unless with Gilbert's syndrome
  • COHORT A: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x ULN
  • COHORT A: International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • COHORT A: Patients must have left ventricular ejection fraction (LVEF) within normal institutional limits within 21 days of starting treatment
  • COHORT A: Patients must have a 12-lead electrocardiogram performed within 2 weeks of treatment start with Fridericia's formula-corrected QT interval (QTcF) =< 450 msec
  • COHORT A: Patients must be able to provide written informed consent
  • COHORT A: Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the first dose
  • COHORT A: Women of childbearing potential and men must agree to use adequate method of contraception for the duration of study participation and for at least 6 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after the last dose of study drug
  • COHORT A: Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, prostate, bladder or melanoma in situ. Patients with prior malignancies must be disease-free for > three years
  • COHORT A: Patients must be able to swallow medication by mouth
  • COHORT B: Patients must be 18 years of age or older on the day of signing informed consent
  • COHORT B: Patients must have histologically proven WHO grade 4 glioblastoma/gliosarcoma, which is progressive or recurrent following radiation therapy +/- chemotherapy
  • COHORT B: Patient initial tumor sample must have wild type IDH with evidence of EGFR mutation/amplification by CLIA-certified laboratory assay. Patients with EGFR mutations in T790M or exon 20 will be excluded
  • COHORT B: Patients may have had no more than two prior recurrences
  • COHORT B: 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 14 days prior to enrollment
  • COHORT B: Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:

  • 12 weeks from the completion of radiation
  • 6 weeks from a nitrosourea chemotherapy
  • 3 weeks from a non-nitrosourea chemotherapy
  • 4 weeks from any investigational (not FDA-approved) agents
  • 4 weeks from the last treatment with bevacizumab
  • 2 weeks from administration of an anti-cancer, non-cytotoxic, FDA-approved agent other than bevacizumab (e.g., hydroxychloroquine, etc.)
  • 1 week from the tumor treating fields device(s)
  • COHORT B: Paraffin embedded tissue must be available from initial surgical resection at diagnosis. The following amount of tissue is requested: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 30 FFPE unstained slides (5um thick).
  • COHORT B: Patients must have a Karnofsky performance status ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • COHORT B: Absolute neutrophil count (ANC) ≥ 1000/uL
  • COHORT B: Platelets ≥ 100000/uL
  • COHORT B: Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/La

  • Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
  • COHORT B: Creatinine < 1.5 times ULN or measured or calculated creatinine clearance > 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (GFR can also be used in place of creatinine or CrCl)

  • Creatinine clearance (CrCl) should be calculated per institutional standard.
  • COHORT B: Total bilirubin ≤ 1.5 x ULN unless with Gilbert's syndrome
  • COHORT B: AST (SGOT) and ALT (SGPT) ≤ 3 x ULN
  • COHORT B: International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • COHORT B: Patients must have left ventricular ejection fraction (LVEF) within normal institutional limits within 21 days of starting treatment
  • COHORT B: Patients must have a 12-lead electrocardiogram performed within 2 weeks of treatment start with QTcF ≤ 450 msec
  • COHORT B: Patients must be able to provide written informed consent
  • COHORT B: Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the first dose
  • COHORT B: Women of childbearing potential and men must agree to use adequate method of contraception for the duration of study participation and for at least 6 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after the last dose of study drug
  • COHORT B: Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, prostate, bladder or melanoma in situ. Patients with prior malignancies must be disease-free for > three years
  • COHORT B: Patients must be able to swallow medication by mouth
  • COHORT C: Patients must be ≥ 70 years of age at the time of informed consent, with a life expectancy > 8 weeks
  • COHORT C: Patients must have histologically proven newly diagnosed WHO grade 4 glioblastoma/gliosarcoma
  • COHORT C: Patient initial tumor sample must have wild type IDH with evidence of EGFR mutation/amplification by CLIA-certified laboratory assay. Patients with EGFR mutations in T790M or exon 20 will be excluded
  • COHORT C: Patient must be able to tolerate MRIs. Pre-study enrollment MRIs must be available for central review, including the pre-surgery MRI and the immediate post-diagnostic surgery MRI. The immediate postoperative MRI is preferred but not required to occur within 96 hours of surgery. The patient must also have a baseline MRI within 14 days prior to enrollment. Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis. Enrollment is at least 2-4 weeks from prior surgery (if time is needed to be extended, PI approval needed)
  • COHORT C: Patients must have a Karnofsky performance status ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • COHORT C: Absolute neutrophil count (ANC) ≥ 1000/uL
  • COHORT C: Platelets ≥ 100000/uL
  • COHORT C: Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/La

  • Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
  • COHORT C: Creatinine < 1.5 times ULN OR measured or calculated creatinine clearance > 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (GFR can also be used in place of creatinine or CrCl)

  • Creatinine clearance (CrCl) should be calculated per institutional standard
  • COHORT C: Total bilirubin ≤ 1.5 x ULN unless with Gilbert's syndrome
  • COHORT C: AST (SGOT) and ALT (SGPT) ≤ 3 x ULN
  • COHORT C: International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • COHORT C: Paraffin embedded tissue must be available from initial surgical resection at diagnosis. The following amount of tissue is requested: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 30 FFPE unstained slides (5um thick)
  • COHORT C: Patients must have left ventricular ejection fraction (LVEF) within normal institutional limits within 21 days of starting treatment
  • COHORT C: Patients must have a 12-lead electrocardiogram performed within 2 weeks of treatment start with QTcF ≤ 450 msec
  • COHORT C: Patients must be able to provide written informed consent
  • COHORT C: Men treated or enrolled on this protocol who has a partner with reproductive potential must agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after the last dose of study drug
  • COHORT C: Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, prostate, bladder or melanoma in situ. Patients with prior malignancies must be disease-free for > three years
  • COHORT C: Patients must be able to swallow medication by mouth

Exclusion Criteria:

  • 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
  • COHORT A: Pregnant women are excluded from this study because ERAS-801 has unknown potential for teratogenic or abortifacients effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ERAS-801, breastfeeding should be discontinued if the mother is treated with ERAS-801
  • COHORT A: Participants currently using or anticipating need to use drugs, food, or herbal supplements known to be strong or moderate inducers or inhibitors of CYP3A4, CYP2C8, and/or CYP2D6 and P-glycoprotein (P-gp) substrates may be enrolled if they have been off the substrates for at least 10 days or 5 half-lives prior to the first dose of ERAS 801, whichever is shorter
  • COHORT A: Participants who have acute or currently active/requiring anti-viral therapy hepatic or biliary disease are ineligible (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases from the primary brain tumor, or stable chronic liver disease per investigator assessment)
  • COHORT A: Patients with gastrointestinal conditions that may affect reliable administration/absorption of medications including difficulty swallowing/unable to swallow pills; malabsorption syndrome; refractory nausea and vomiting, chronic gastrointestinal (GI) disease or previous significant bowel resection with clinically significant sequelae are ineligible
  • COHORT A: Participants receiving P-gp inhibitors are ineligible
  • COHORT A: Patients who have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial are ineligible
  • COHORT B: Participants may not be receiving any other investigational agents
  • COHORT B: Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ERAS-801 are ineligible
  • COHORT B: 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 PI
  • COHORT B: 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 B: Participants must not have evidence of significant hematologic, renal, or hepatic dysfunction
  • COHORT B: Participants must not have evidence of significant intracranial hemorrhage
  • COHORT B: 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 B: 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
  • COHORT B: Pregnant women are excluded from this study because ERAS-801 has unknown potential for teratogenic or abortifacients effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ERAS-801, breastfeeding should be discontinued if the mother is treated with ERAS-801
  • COHORT B: Participants currently using or anticipating need to use drugs, food, or herbal supplements known to be strong or moderate inducers or inhibitors of CYP3A4, CYP2C8, and/or CYP2D6 and P-gp substrates may be enrolled if they have been off the substrates for at least 10 days or 5 half-lives prior to the first dose of ERAS 801, whichever is shorter
  • COHORT B: Participants who have acute or currently active/requiring anti-viral therapy hepatic or biliary disease are ineligible (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases from the primary brain tumor, or stable chronic liver disease per investigator assessment)
  • COHORT B: Patients with gastrointestinal conditions that may affect reliable administration/absorption of medications including difficulty swallowing/unable to swallow pills; malabsorption syndrome; refractory nausea and vomiting, chronic gastrointestinal (G

Study Design

Enrollment

50 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort A (ERAS-801)

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.

experimental: Cohort B (ERAS-801)

After 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.

experimental: Cohort C (ERAS-801)

Within 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

Biospecimen Collection

Undergo urine, blood, and CSF sample collection

Echocardiography Test

Undergo ECHO

EGFR Inhibitor ERAS-801

Given PO

Fludeoxyglucose F-18

Given FDG

Magnetic Resonance Imaging

Undergo brain MRI

Positron Emission Tomography

Undergo FDG PET

Surgical Procedure

Undergo surgical resection

Primary outcome measure

  • Fludeoxyglucose F-18 (FDG) tumor uptake (Cohort A) [ Time Frame: At baseline, prior to initiation of study treatment and after study treatment prior to surgery ]
  • Pharmacokinetics (PK) dose modification (Cohort B) [ Time Frame: At day 1 and day 15 ]
  • 6 month progression free survival (Cohort C) [ Time Frame: At 6 months ]

Central Contacts and Locations

Locations

UCLA / Jonsson Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90095

Contacts

Phioanh (. Nghiemphu

310-825-5321pnghiemphu@mednet.ucla.edu

Principal Investigator:

Phioanh Nghiemphu

More Information

Sponsor

Jonsson Comprehensive Cancer Center

Last update posted

Jul 20, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Jonsson Comprehensive Cancer Center on 2026-07-20.