Temozolomide, With or Without WSD0922-FU, for the Treatment of EGFR-Mutant, IDH-Wildtype Glioblastoma

Randomized Phase II Trial to Evaluate the Efficacy of WSD0922-FU When Combined With Adjuvant Temozolomide in Patients With EGFR Mutant Glioblastoma

This phase II trial compares the effect of adding WSD0922-FU to temozolomide versus temozolomide alone in slowing disease progression in patients with Epidermal Growth Factor Receptor (EGFR)-mutant, IDH-wildtype glioblastoma. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. WSD0922-FU is a targeted treatment which blocks EGFR. It is able to get into the brain and spinal cord and help treat those types of tumors. Adding WSD0922-FU to the usual treatment with temozolomide may be more effective in slowing disease progression, compared to temozolomide alone, in patients with EGFR-mutant, IDH-wildtype glioblastoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma, IDH-Wildtype
• Intervention / Treatment: Drug: Temozolomide; Procedure: Chest Radiography; Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU; Procedure: Magnetic Resonance Imaging; Procedure: Echocardiography Test; Procedure: Archive Sample Retrieval; Procedure: Biospecimen Collection

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
• Study Contact Backup: Name: Cancer Center Clinical Trials; Phone Number: 507-293-6386

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
      • Contact: Cancer Center Clinical Trials; Phone Number: 507-293-6386
      • Principal Investigator: Shannon P Fortin Ensign, MD, PhD
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
      • Principal Investigator: Wendy J. Sherman, MD
      • Contact: Cancer Center Clinical Trials; Phone Number: 507-293-6386
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
      • Contact: Cancer Center Clinical Trials; Phone Number: 507-293-6386
      • Principal Investigator: Sani H. Kizilbash, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >= 18 years

• Histopathologic diagnosis of glioblastoma, IDH-wildtype [as defined by the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors] on primary pathology review

  • NOTE: MGMT promoter methylation status must have been performed

• Glioblastomas must have a pathogenic EGFR mutation, with or without EGFR amplification, detected by Clinical Laboratory Improvement Act (CLIA)-certified next-generation sequencing

  • EGFR mutation includes both deoxyribonucleic acid (DNA) sequence variants (e.g. point mutations, etc.) and transcript variants (e.g. EGFRvIII, etc.)
  • EXCEPTIONS: Glioblastomas which are EGFR wildtype with amplification are excluded. Glioblastomas which only have EGFR variants of unknown significance (without any pathogenic EGFR mutations) are also excluded

• Patients must have completed standard radiation (60 Gy in 30 fractions) with concurrent temozolomide (missing no more than 2 weeks of temozolomide), and adequately recovered from treatment related toxicities

  • NOTE: Adjuvant temozolomide must not have been initiated
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Hemoglobin > 9.0 g/dL (obtained =< 14 days prior to registration)
• Leukocytes > 3.0 x 10^9/L (obtained =< 14 days prior to registration)
• Absolute neutrophil count (ANC) > 1.5 x 10^9/L (obtained =< 14 days prior to registration)
• Platelet count > 100 x 10^9/L (obtained =< 14 days prior to registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (< 3 x ULN for patients with Gilbert's disease) (obtained =< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained =< 14 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained =< 14 days prior to registration)
• Calculated creatinine clearance >= 45 mL/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration)
• Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
• Provide written informed consent
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Must be willing to take light-protective measures during the study and for two weeks after last dose of WSD0922-FU
• Willingness to provide mandatory tissue specimens for correlative research

Exclusion Criteria:

• Patients deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field

  • EXCEPTION: Patients deemed to have pseudoprogression are eligible; however, this should be controlled on =< 4 mg of dexamethasone and should not require bevacizumab at study onset

• Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown:

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential (and persons able to father a child) who are unwilling to employ adequate contraception

• Any of the following prior therapies:

  • Surgery for glioblastoma =< 3 weeks prior to registration
  • Radiation therapy =< 2 weeks prior to registration

  • Systemic therapies intended for the management of the glioblastoma, including but not limited to:

    • Targeted therapies
    • EGFR inhibitors
    • Alkylating chemotherapy
    • Adjuvant temozolomide (note that temozolomide administered concurrent with radiation is NOT an exclusion criterion)
    • Immunotherapy
    • Biologics
    • Any other systemic therapies [Food and Drug Administration (FDA) approved, off-label, investigational]
    • Bevacizumab
  • Non-enzyme-inducing anticonvulsants < 2 weeks prior to registration
  • Strong inducers and strong inhibitors of CYP3A < 14 days prior to registration

• Failure to adequately recover from any adverse events or complications related to any of the following therapies received prior to registration:

  • Craniotomy and resection of tumor
  • Stereotactic biopsy of tumor
  • Other major surgical procedure
  • Radiation therapy < 2 weeks prior to registration
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. Examples include (but are not limited to) refractory nausea and vomiting (if not controlled by supportive therapy), inability to swallow the formulated product, previous significant bowel resection, other chronic gastrointestinal diseases, etc

• Uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection
  • Severe skin lesions such as skin/pressure ulcers, chronic leg ulcers or non-healing wounds.
  • Active history of keratitis
  • Symptomatic CNS complications that require urgent neurosurgical or medical (e.g. mannitol) intervention
  • Known intracranial hemorrhage which is unrelated to tumor
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
  • Or psychiatric illness/social situations that would limit compliance with study requirements

• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy

  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Other active malignancy within the last 3 years that would interfere with treatment on this protocol

  • EXCEPTIONS: non-melanoma skin cancer, carcinoma in situ of the cervix, patients on hormonal therapy for treated breast or prostate cancer
• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (temozolomide, WSD0922-FU); Patients receive temozolomide PO QD on days 1-5 of cycles 1-6 and WSD0922-FU PO BID on days 1-5, 8-12, 15-19, and 22-26 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease recurrence while on therapy and are planning to undergo tumor resection or stereotactic biopsy prior to starting alternative treatment continue receiving WSD0922-FU PO BID on days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle until the time of surgery. Patients also undergo ECHO and MRI throughout the trial and undergo chest x-ray and collection of tissue samples on study. Patients may undergo optional collection of blood and/or cerebrospinal fluid (CSF) samples throughout the trial.	Drug: Temozolomide; Given PO; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; TMZ; CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Gliotem; Temizole; Procedure: Chest Radiography; Undergo chest x-ray; Other Names: Chest X-ray; Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU; Given PO; Other Names: BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU; EGFR Mutant Inhibitor WSD0922-FU; WSD 0922-FU; WSD-0922-FU; WSD0922-FU; Procedure: Magnetic Resonance Imaging; Undergo brain MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Echocardiography Test; Undergo ECHO; Other Names: Echocardiography; EC; Procedure: Archive Sample Retrieval; Archived tumor specimens will be retrieved if available from original surgery for glioblastoma.; Procedure: Biospecimen Collection; Undergo collection of blood, cerebrospinal fluid (CSF), and/or tumor tissue samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection
Active Comparator: Arm B (temozolomide); Patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience disease recurrence while on therapy and are planning to undergo tumor resection or stereotactic biopsy prior to starting alternative treatment may initiate WSD0922-FU PO BID on days 1-5, 8-12, 15-19, and 22-26 of each cycle. Cycles repeat every 28 days until the time of surgery. Patients also undergo ECHO and MRI throughout the trial and undergo chest x-ray and collection of tissue samples on study. Patients may undergo optional collection of blood and/or CSF samples throughout the trial.	Drug: Temozolomide; Given PO; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; TMZ; CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Gliotem; Temizole; Procedure: Chest Radiography; Undergo chest x-ray; Other Names: Chest X-ray; Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU; Given PO; Other Names: BBB Penetrable EGFR/EGFRvIII Inhibitor WSD0922-FU; EGFR Mutant Inhibitor WSD0922-FU; WSD 0922-FU; WSD-0922-FU; WSD0922-FU; Procedure: Magnetic Resonance Imaging; Undergo brain MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Echocardiography Test; Undergo ECHO; Other Names: Echocardiography; EC; Procedure: Archive Sample Retrieval; Archived tumor specimens will be retrieved if available from original surgery for glioblastoma.; Procedure: Biospecimen Collection; Undergo collection of blood, cerebrospinal fluid (CSF), and/or tumor tissue samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Defined as the time from randomization to the time of documented disease progression or death. PFS will be evaluated for each arm, where patients will be evaluated based on the treatment arm to which they were randomized and will include only those who are eligible and have received any protocol therapy to be considered evaluable. PFS distributions will be graphically and quantitatively compared using Kaplan-Meier methods. These methods will be used to estimate the median PFS as well as 1-year estimates for PFS by treatment arm along with corresponding 95% confidence intervals. Cox proportional hazards models will also be used to assess influential factors on PFS both in the univariate and the multivariable settings.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (safety and tolerability)	Safety and tolerability will be evaluated by treatment regimen. Adverse events (AEs) will be summarized per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 , and where toxicities will be defined as adverse events that are deemed to be at least possibly treatment-related (i.e., attribution of "possibly", "probably", or "definite"). The maximum grade for each type of treatment-related AE will be recorded for each patient, and the frequency of each will be summarized by treatment arm. Frequency tables and graphical evaluations of AEs and treatment-related AEs will be summarized and evaluated to assess if there are any patterns or differences in the rates or types of AEs.	Up to 30 days after last dose
Overall survival	Defined as the time from randomization to the time of death. Kaplan Meier methods will be used to estimate key aspects of the overall survival distributions for each of the treatment arms, and log rank tests will be used to compare these distributions between arms. If patients randomized to the control arm choose to receive WSD0922-FU upon documented recurrence/progressive disease, then will also utilize more complex approaches to evaluate overall survival that accommodates different time periods of receiving treatment.	Up to 5 years
Overall response rate (ORR)	The objective response classifications and best responses observed for patients will be summarized by treatment arm. These will be classified based on review as the proportion of patients who achieve any response to treatment (ORR, including minor, partial, or complete response) as well as those who achieve a partial or complete response to therapy divided by the total number of patients randomized and treated on that arm. Assuming that the number of patients who respond to therapy on each arm is binomially distributed, will estimate these proportions along with corresponding 95% confidence intervals.	Up to 5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Sani H. Kizilbash, MD, MPH, Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): August 16, 2026
• Primary Completion (Estimated): July 31, 2036
• Study Completion (Estimated): July 31, 2036

Study Registration Dates

• First Submitted: July 13, 2026
• First Submitted That Met QC Criteria: July 13, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Azoles; Physical Phenomena; Dacarbazine; Triazenes; Imidazoles; Chemistry Techniques, Analytical; Spectrum Analysis; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Temozolomide; Specimen Handling; Magnetic Resonance Spectroscopy; X-Rays
• Other Study ID Numbers: MC250711; 26-000481 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No