Clinical Trials /

Bispecific T Cell Engager BRiTE for Patients With Grade IV Malignant Glioma

NCT04903795

Description:

This is a phase 1 study of hEGFRvIII-CD3-biscFv Bispecific T cell engager (BRiTE) in patients diagnosed with World Health Organization (WHO) grade IV malignant glioma (MG). The primary objective is to evaluate the safety of BRiTE alone and in combination with peripheral autologous T-cell infusion in patients whose MG has an EGFR (epidermal growth factor receptor) variant III (EGVRvIII) mutation.

Related Conditions:
  • Malignant Glioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Bispecific T Cell Engager BRiTE for Patients With Grade IV Malignant Glioma
  • Official Title: A Phase I Study of hEGFRvIII-CD3 Bi-scFv (BRiTE) in Patients With WHO Grade IV Malignant Glioma

Clinical Trial IDs

  • ORG STUDY ID: Pro00108079
  • NCT ID: NCT04903795

Conditions

  • Malignant Glioma
  • Glioblastoma

Interventions

DrugSynonymsArms
hEGFRvIII-CD3 (BRiTE)BRiTEhEGFRvIII-CD3 (BRiTE) with and without peripheral autologous T-cell (ACT) infusion
Activated Cell TherapyACThEGFRvIII-CD3 (BRiTE) with and without peripheral autologous T-cell (ACT) infusion

Purpose

This is a phase 1 study of hEGFRvIII-CD3-biscFv Bispecific T cell engager (BRiTE) in patients diagnosed with World Health Organization (WHO) grade IV malignant glioma (MG). The primary objective is to evaluate the safety of BRiTE alone and in combination with peripheral autologous T-cell infusion in patients whose MG has an EGFR (epidermal growth factor receptor) variant III (EGVRvIII) mutation.

Detailed Description

      A maximum of eighteen patients will participate in this study after undergoing undergoing
      standard of care radiation therapy (XRT) with or without concomitant temozolomide (TMZ).
      Patients will undergo a leukapheresis to generate autologous lymphocytes that may be infused
      prior to BRiTE injection, pending tolerance of the BRiTE only injection. For newly diagnosed
      patients, leukapheresis will occur either before initiating radiation therapy or after
      completing radiation therapy, but before initiating adjuvant temozolomide. After completion
      of a minimum of six cycles of adjuvant temozolomide, or at first progression, eligible
      patients will receive a bolus BRiTE injection followed by a 14-day safety monitoring period.
      If no dose limiting toxicity (DLT) or unacceptable toxicity occurs within 14 days, patients
      will receive an infusion of activated cell therapy (ACT) derived from autologous lymphocytes
      immediately followed by a second bolus BRiTE injection.
    

Trial Arms

NameTypeDescriptionInterventions
hEGFRvIII-CD3 (BRiTE) with and without peripheral autologous T-cell (ACT) infusionExperimentalFour escalating doses of BRiTE are planned: #1: 57.0 ng/kg, #2: 570.0 ng/kg, #3: 5700.0 ng/kg, and #4: 57000.0 ng/kg. With the second injection of BRiTE, patients will each receive 3 x 10^7 T-cells per kg.
  • hEGFRvIII-CD3 (BRiTE)
  • Activated Cell Therapy

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years old

          -  Pathologically documented supratentorial WHO grade IV malignant glioma with an
             EGFRvIII mutation confirmed by Caris (at most recent diagnosis)

               1. If patient is newly diagnosed, the patient must have completed standard of care
                  radiation therapy (3 or 6 week courses are accepted) with or without
                  temozolomide. i. Patients with methylated MGMT promoter status need to initiate
                  or complete 6 cycles of adjuvant temozolomide to be eligible. ii. Patients with
                  an unmethylated MGMT promoter status do not need to initiate or complete adjuvant
                  temozolomide to be eligible

               2. If patient is at first progression, the patient must have radiographic evidence
                  of progression and completed a standard of care regimen of radiation therapy with
                  or without chemotherapy and initiated adjuvant chemotherapy. Note: Imaging must
                  be completed within 14 days of enrollment.

               3. Patients who progress during XRT or within 4 weeks after completion of XRT are
                  not eligible.

          -  Karnofsky Performance Score (KPS) ≥ 70%

          -  Absolute neutrophil count (ANC) ≥ 1000/mm3

          -  Platelet count ≥ 100,000

          -  Hemoglobin ≥ 9.0 g/dL

          -  Creatinine ≤ 1.2 x normal range

          -  Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) ≤ 2.5 x ULN

          -  Total bilirubin ≤ 2 x ULN (Exception: Patient has known Gilbert's Syndrome or patient
             has suspected Gilbert's Syndrome, for which additional lab testing of direct and/or
             indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤
             3.0 x ULN is acceptable.))

          -  For women of childbearing potential: negative serum pregnancy test within 1 week of
             1st BRiTE injection.

        Exclusion Criteria:

          -  Women who are pregnant of breastfeeding

          -  History or evidence of central nervous system bleeding as defined by stroke or
             intraocular bleed (including embolic stroke) not associated with any antitumor surgery
             within 6 months before enrollment

          -  Known hypersensitivity to immunoglobulins or to any other component of the BRiTE

          -  Prior malignancy (other than in situ cancer) unless treated with curative intent and
             without evidence of disease for > 2 years before screening

          -  Infection requiring intravenous antibiotics that was completed < 1 week of study
             enrollment (day 1) with the exemption of prophylactic antibiotics for long line
             insertion or biopsy

          -  Known positive test for human immunodeficiency virus (HIV)

          -  Known active hepatitis B or C infection

          -  Toxicities from prior antitumor therapy have not resolved to CTCAE version 5 grade 1
             (with the exception of adverse events reflecting myelosuppression such as neutropenia,
             anemia, or thrombocytopenia), or to levels dictated in the eligibility criteria.
             Exceptions include: alopecia or toxicities from prior antitumor therapy that are
             considered irreversible (defined as having been present and stable for > 2 months) are
             allowed if they are not otherwise described in the exclusion criteria

          -  Patients on corticosteroids ≥ 2 mg dexamethasone daily or equivalent within 14 days of
             1st BRiTE injection

          -  Females of reproductive potential and males who are unwilling to practice an
             acceptable method(s) of effective birth control while on study through 1 week (5
             half-lives) after receiving the last dose of study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicity (DLT)
Time Frame:Begins when first BRiTE injection is given and goes through 28 days after the 2nd BRiTE injection
Safety Issue:
Description:Proportion of patients with DLT within each dose level

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:7 weeks
Safety Issue:
Description:ORR per modified Response Assessment in Neuro-Oncology Criteria (RANO)
Measure:Pharmacokinetic (PK) of BRiTe observed during the first injection of BRiTE as measured by time (in minutes)
Time Frame:96 hours post BRiTE injection
Safety Issue:
Description:Time for the concentration of BRITE to reach half of the level initially administered
Measure:Pharmacokinetic (PK) of BRiTe administered with ACT as measured by time (in minutes)
Time Frame:96 hours post BRiTE injection
Safety Issue:
Description:Time for the concentration of BRITE to reach half of the level initially administered

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Duke University

Trial Keywords

  • EGFRvIII
  • Khasraw
  • BRiTE
  • Pro00108079

Last Updated

May 27, 2021