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CART-EGFRvIII + Pembrolizumab in GBM

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. One of the following diagnoses of GBM: a. Newly diagnosed glioblastoma multiforme that is histologically confirmed by pathology review of surgically resected tissue; OR b. An integrated molecular/pathologic diagnosis of diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade
  • IV. This diagnosis requires patients have one of the following: i.
High-level amplification of EGFR; OR ii. Combined whole chromosome 7 gain and whole chromosome 10 loss (+7/-10); OR iii. TERT promoter mutation. 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.

Exclusion Criteria:

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 infection. 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 reactions. 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. 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 physician-investigator. 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 physician-investigator. 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. 13. Patients with tumors primarily localized to the brain stem or spinal cord.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03726515
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Pennsylvania
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Donald O'Rourke, MD
Principal Investigator Affiliation Abramson Cancer Center at Penn Medicine
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma
Arms & Interventions

Arms

Experimental: CART-EGFRvIII + Pembrolizumab

Interventions

Biological: - CART-EGFRvIII T cells

autologous T cells that have been engineered to express an extracellular Humanized single chain antibody (scFv) with specificity for EGFRvIII linked to an intracellular signaling molecule comprised of a tandem signaling domain of the 4-1BB and TCRζ signaling modules.

Biological: - Pembrolizumab

humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Philadelphia, Pennsylvania

Status

Address

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104