Phase I EGFR BATs in Newly Diagnosed Glioblastoma

NCT03344250 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 20105
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioblastoma; Glioblastoma Multiforme

Keywords

Adoptive Cell Therapy; Armed Activated T-cells; Bispecific Antibodies; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

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

  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 (14)

• Immune measures in blood- cellular phenotype

  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

• Immune measures in blood- interferon-γ

  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

• Immune measures in blood- EliSpots

  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

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

  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

• Immune measures in blood- serum cytokine patterns

  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

Study Arms (2)

Main Study

EXPERIMENTAL

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

Subcohort for MGMT unmethylated patients

EXPERIMENTAL

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

EGFR BATs with TMZ following SOC RT/TMZ DRUG

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.

Main Study

Weekly EGFR BATs following SOC RT/TMZ DRUG

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

Subcohort for MGMT unmethylated patients

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed newly diagnosed intracranial GBM or gliosarcoma
• Age ≥ 18 years.
• Karnofsky Performance Status ≥ 60.
• Be willing and able to provide written informed consent for the trial.
• 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.
• Females of childbearing potential, and males, must be willing to use an effective method of contraception
• 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.
• 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

You may not qualify if:

• 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.
• Patients with evidence of leptomeningeal dissemination or subependymal spread on initial MRI.
• Patients with extracranial metastases.
• Known hypersensitivity to cetuximab or other EGFR antibody.
• Alpha 1,3 Galactose IgE ("alpha gal") test result outside of the reference range (indicating likely hypersensitivity to cetuximab)
• Evidence of active bleeding or bleeding diathesis.
• 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).
• 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).
• Has received a live vaccine within 30 days of planned start of study therapy.
• Has received any treatment for GBM besides surgery.
• Females must not be breastfeeding.
• 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.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

Samantha Brooks

Charlottesville, Virginia, 22908, United States

Location

Related Publications (3)

• 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.

  PMID: 25688159 BACKGROUND

• 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.

  PMID: 25802762 BACKGROUND

• Fadul CE, Thakur A, Kim J, Kassay-McAllister J, Schalk D, Lopes MB, Donahue J, Purow B, Dillon P, Le T, Schiff D, Liu Q, Lum LG. Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide. J Neurooncol. 2024 Jan;166(2):321-330. doi: 10.1007/s11060-024-04564-y. Epub 2024 Jan 23.

  PMID: 38263486 DERIVED

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Camilo Fadul, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: EGFR BATs administered in combination with standard of care temozolomide and radiation

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 17, 2017
• Study Start: March 1, 2018
• Primary Completion: December 8, 2021
• Study Completion: May 8, 2023
• Last Updated: March 6, 2025

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)