This is an open-label, phase 1 study to assess the safety and tolerability of EGFRvIII T
cells in combination with pembrolizumab (PD-1 Inhibitor) in patients with newly diagnosed,
EGFRvIII+, MGMT-unmethylated glioblastoma.
1. Newly diagnosed glioblastoma (GBM) that is histologically confirmed by pathology
review of surgically resected tissue.
2. Undergone tumor resection.
3. No prior systemic therapies, radiation, tumor-treating fields, or intratumoral
therapeutic agents including Gliadel wafers are allowed. Tumor resection must be the
only tumor-directed treatment that the patient has received for glioboblastoma.
4. Tumor tissue is positive for EGFRvIII expression, as performed by either the
University of Pennsylvania's in-house fusion transcript panel (RNA-based assay using
Illumina HiSeq platform) or NeoGenomics Laboratories (quantitative RT-PCR assay).
5. Tumor tissue is negative for MGMT promoter methylation (i.e. the tumor is
MGMT-unmethylated), as performed by either the University of Pennsylvania's in-house
pyrosequencing protocol or NeoGenomics Laboratories.
6. Patients ≥ 18 years of age
7. ECOG performance status 0-1
8. Provides written informed consent
9. Must have adequate organ function as measured by:
1. White blood count ≥ 2500/mm3; platelets ≥ 100,000/mm3, hemoglobin ≥ 9.0 g/dL;
without transfusion or growth factor support
2. AST, ALT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total
bilirubin ≤ 2.0 mg/dL
3. Serum creatinine < 1.5 x upper limit of normal
4. Adequate cardiac function (LVEF ≥ 45%)
10. Subjects of reproductive potential must agree to use acceptable birth control methods.
1. Pregnant or lactating women
2. Inadequate venous access for or contraindications to leukapheresis.
3. Active Hepatitis B, hepatitis C, or HIV infection, or other active, uncontrolled
4. History of allergy or hypersensitivity to study product excipients (human serum
albumin, DMSO, and Dextran 40)
5. History of severe hypersensitivity reactions to other monoclonal antibodies which in
the opinion of the investigator may post an increased risk of serious infusion
6. Requirement for immunosuppressive agents including but not limited to cyclosporine,
MMF, tacrolimus, rapamycin, or anti-TNF agents within 4 weeks of eligibility
confirmation by the physician-investigator.
7. Subjects with a history of known or suspected, severe or uncontrolled autoimmune or
connective tissue disease. Patients with vitiligo, controlled type 1 diabetes mellitus
(on stable insulin dose), residual autoimmune-related hypothyroidism (due to
autoimmune condition only requiring hormone replacement), or psoriasis (not requiring
systemic treatment), or conditions not expected to recur in the absence of an external
trigger, are permitted to enroll.
8. Known history or current interstitial lung disease or non-infectious pneumonitis
9. Prior allogenic bone marrow or solid organ transplant
10. Any concurrent malignancy other than non-melanoma skin cancer that has been curatively
treated, or carcinoma in situ of the cervix or bladder that has been curatively
treated. For any prior invasive malignancy, at least 5 years must have elapsed since
curative therapy and patients must not have received any radiation to the brain.
Monoclonal gammopathy of undetermined significance (MGUS) is permitted.
11. Any uncontrolled active medical or psychiatric disorder that would preclude
participation as outlined.
12. Severe, active co-morbidity in the opinion of the physician-investigator would
preclude participation in this study, including but not limited to the following:
1. Unstable angina within 6 months prior to eligibility confirmation by the
2. Transmural myocardial infarction within the last 6 months prior to eligibility
confirmation by the physician-investigator
3. New York Heart Association grade II or greater congestive heart failure requiring
hospitalization within 12 months prior to eligibility confirmation by the
4. Serious and inadequately controlled cardiac arrhythmia
5. Serious or non-healing wound, ulcer, or history of abdominal fistula,
gastrointestinal perforation, intra-abdominal abscess major surgical procedure,
open biopsy, or significant traumatic injury within 28 days prior to eligibility
confirmation by the physician-investigator, with the exception of the craniotomy
for tumor resection.
12. Patients with tumors primarily localized to the brain stem or spinal cord.