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.
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
Drug | Synonyms | Arms |
---|
hEGFRvIII-CD3 (BRiTE) | BRiTE | hEGFRvIII-CD3 (BRiTE) with and without peripheral autologous T-cell (ACT) infusion |
Activated Cell Therapy | ACT | hEGFRvIII-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
Name | Type | Description | Interventions |
---|
hEGFRvIII-CD3 (BRiTE) with and without peripheral autologous T-cell (ACT) infusion | Experimental | Four 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