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CompletedNCT03344250Updated Mar 6, 2025

Phase I EGFR BATs in Newly Diagnosed Glioblastoma

A Phase 1 interventional study of EGFR BATs with TMZ following SOC RT/TMZ and Weekly EGFR BATs following SOC RT/TMZ in Glioblastoma and Glioblastoma Multiforme, sponsored by University of Virginia. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-06.

Sponsored by University of Virginia · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
16
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
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Study summary

This is a phase I trial using EGFR Bi-armed Activated T-cells (BATs) in combination with standard of care temozolomide (TMZ) and radiation (RT) in patients with glioblastoma (GBM). The purpose of the study is to determine a safe dose of EGFR BATs when given with standard of care therapy.

Read the detailed description

In addition to finding the safe dose of EGFR BATs, immune evaluations will be performed as delineated in the schedule of events to measure immune responses during all stages of treatment for GBM.

02

Conditions studied

  • Glioblastoma
  • Glioblastoma Multiforme

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Keywords

  • Adoptive Cell Therapy
  • Armed Activated T-cells
  • Bispecific Antibodies
  • Immunotherapy
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Histologically-confirmed newly diagnosed intracranial GBM or gliosarcoma
  2. Age ≥ 18 years.
  3. Karnofsky Performance Status ≥ 60.
  4. Be willing and able to provide written informed consent for the trial.
  5. For patients with resection, CT/MRI with contrast must be performed within 72 hours following resection. Intraoperative post resection MRI is acceptable. No post surgery CT/MRI is required for patients who have received biopsy.
  6. Females of childbearing potential, and males, must be willing to use an effective method of contraception
  7. Females of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  8. Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days prior to apheresis.

Absolute lymphocyte count ≥ 500/mm3, Absolute neutrophil count (ANC) ≥1,000 /mcL, Platelets ≥ 100,000 / mcL, Hemoglobin ≥ 9 g/dL (or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment), BUN ≤ 1.5 X upper limit of normal (ULN), Serum creatinine within the normal limits OR Measured or calculated creatinine clearance ≥60 mL/min/1.73m2, Serum total bilirubin ≤ 1.5 X ULN OR AST (SGOT) and ALT (SGPT) ≤ 5 X ULN, Albumin >2.5 mg/dL, International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN, unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

i. Additional inclusion criteria for sub-cohort: MGMT unmethylated according to UVA pathology testing

Exclusion criteria

Exclusion Criteria:

  1. Patients with a diagnosis of another malignancy within 3 years of being on-study. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Patients must not be on any treatment for another malignancy.
  2. Patients with evidence of leptomeningeal dissemination or subependymal spread on initial MRI.
  3. Patients with extracranial metastases.
  4. Known hypersensitivity to cetuximab or other EGFR antibody.
  5. Alpha 1,3 Galactose IgE ("alpha gal") test result outside of the reference range (indicating likely hypersensitivity to cetuximab)
  6. Evidence of active bleeding or bleeding diathesis.
  7. Cardiac Status: Patients will be ineligible for treatment on this protocol if (prior to protocol entry):

    There is a history of a recent (within one year) myocardial infarction or stroke.

    There is a current or prior history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF \< 45% by MUGA or ECHO).

    There is clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA or ECHO results).

  8. Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  9. Has received a live vaccine within 30 days of planned start of study therapy.
  10. Has received any treatment for GBM besides surgery.
  11. Females must not be breastfeeding.
  12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  13. A patient may be excluded if, in the opinion of the treating clinician, the patient is not capable of being compliant.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
16 participants (actual)

Study arms

  • Experimental
    Main Study

    Study participants will have cells collected by leukapheresis prior to initiating standard concurrent RT and TMZ. Participants will receive the first and second infusions of EGFR BATs on days 14 and 21 after finishing concurrent RT and TMZ and then receive an infusion on day 21 of the first six cycles of TMZ.

    Drug: EGFR BATs with TMZ following SOC RT/TMZ

  • Experimental
    Subcohort for MGMT unmethylated patients

    Study participants will have cells collected by leukapheresis prior to initiating standard concurrent RT and TMZ. About 4 weeks after completion of RT/TMZ, participants will receive 8 weekly doses of EGFR BATs.

    Drug: Weekly EGFR BATs following SOC RT/TMZ

Interventions

  • DrugEGFR BATs with TMZ following SOC RT/TMZ

    Standard of care: 6 weeks of RT and TMZ and 6 cycles of TMZ (150-200 mg/m2) on days 1-5 of each 28 day cycle Experimental: EGFR BATs 2 and 3 weeks after completing RT, and then on day 21 of each cycle of TMZ.

  • DrugWeekly EGFR BATs following SOC RT/TMZ

    Standard of care: 6 weeks of RT and TMZ Experimental: 8 weekly doses of EGFR BATs following SOC RT and TMZ

05

What researchers measure

Primary outcomes

  1. Maximum tolerated dose

    Maximum tolerated dose will be based on number of dose limiting toxicities at each dose level

    Time frame: The study will not advance to the next dose until 7 days after the last patient in the cohort completes his or her second infusion of EGFR BATs

Secondary outcomes

  1. Immune measures in blood- cellular phenotype

    Sequential monitoring of cellular phenotype

    Time frame: Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion

  2. Immune measures in blood- interferon-γ

    Sequential monitoring of interferon-γ

    Time frame: Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion

  3. Immune measures in blood- EliSpots

    Sequential monitoring of EliSpots

    Time frame: Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion

  4. Immune measures in blood- anti-GBM cytotoxicity of peripheral blood mononuclear cells directed at GBM cell lines

    Sequential monitoring of anti-GBM cytotoxicity of peripheral blood mononuclear cells directed at GBM cell lines

    Time frame: Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion

  5. Immune measures in blood- serum cytokine patterns

    Sequential monitoring of serum cytokine patterns

    Time frame: Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion

  6. Immune measures in blood- anti-GBM antibodies

    Sequential monitoring of anti-GBM antibodies

    Time frame: Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion

  7. Clinical response

    Progression-free survival (PFS)

    Time frame: Every 3 months following last study visit until death or study closure, expected within 5 years

  8. Survival

    Overall Survival (OS)

    Time frame: Every 3 months following last study visit until death or study closure, expected within 5 years

  9. Response Rate

    Objective Response Rate

    Time frame: Every 3 months following last study visit until death or study closure, expected within 5 years

  10. Correlation of imaging to PFS and OS

    Imaging (extent of resection) will be evaluated for correlation with PFS and OS.

    Time frame: Up to 12 months after study treatment completion

  11. Correlation of pathology to PFS and OS

    EGFR expression and tumor-infiltrating lymphocytes and age will be evaluated for correlation with PFS and OS.

    Time frame: Up to 12 months after study treatment completion

  12. Correlation of clinical response to PFS and OS

    Steroid use at the time of leukapheresis and age will be evaluated for correlation with PFS and OS.

    Time frame: Up to 12 months after study treatment completion

  13. Correlation of immune response to PFS and OS

    Immune response characteristics will be evaluated for correlation with PFS and OS.

    Time frame: Up to 12 months after study treatment completion

  14. Adverse events, including dose limiting toxicities

    Safety of 8 weekly doses of BATs in unmethylated MGMT patients without adjuvant temozolomide

    Time frame: Through 30 days following last dose of EGFR BATs

06

Study locations

1 site
  • Samantha Brooks
    Charlottesville, Virginia 22908, United States
07

References and documents

Publications

  • Lum LG, Thakur A, Al-Kadhimi Z, Colvin GA, Cummings FJ, Legare RD, Dizon DS, Kouttab N, Maizel A, Colaiace W, Liu Q, Rathore R. Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial. Clin Cancer Res. 2015 May 15;21(10):2305-14. doi: 10.1158/1078-0432.CCR-14-2280. Epub 2015 Feb 16. PubMed 25688159 ↗
  • Vaishampayan U, Thakur A, Rathore R, Kouttab N, Lum LG. Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients. Prostate Cancer. 2015;2015:285193. doi: 10.1155/2015/285193. Epub 2015 Feb 23. PubMed 25802762 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03344250
Lead sponsor
University of Virginia
Responsible party
Camilo E. Fadul, MD (Professor, University of Virginia) — Principal investigator
First posted
Nov 17, 2017
Start date
Mar 1, 2018
Primary completion
Dec 8, 2021
Completion
May 8, 2023
Last update
Mar 6, 2025

Study contacts

Camilo Fadul, MD
principal investigator · University of Virginia

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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