GlioblastomaPhase 1NCT03726515
CART-EGFRvIII + Pembrolizumab in GBM
A Phase 1 study testing CART-EGFRvIII T cells and Pembrolizumab in people with Glioblastoma, run by University of Pennsylvania at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- CART-EGFRvIII T cells and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2019to 27 Feb 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- One of the following diagnoses of GBM:
- 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.
- Undergone tumor resection.
- 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.
- 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).
- 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.
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- Patients ≥ 18 years of age
- ECOG performance status 0-1
- Provides written informed consent
- Must have adequate organ function as measured by:
- White blood count ≥ 2500/mm3; platelets ≥ 100,000/mm3, hemoglobin ≥ 9.0 g/dL; without transfusion or growth factor support
- AST, ALT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin ≤ 2.0 mg/dL
- Serum creatinine < 1.5 x upper limit of normal
- Adequate cardiac function (LVEF ≥ 45%)
- Subjects of reproductive potential must agree to use acceptable birth control methods.
Who cannot join
- Pregnant or lactating women
- Inadequate venous access for or contraindications to leukapheresis.
- Active Hepatitis B, hepatitis C, or HIV infection, or other active, uncontrolled infection
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- 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.
- 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.
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- 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.
- Known history or current interstitial lung disease or non-infectious pneumonitis
- 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:
- Unstable angina within 6 months prior to eligibility confirmation by the physician-investigator
- Transmural myocardial infarction within the last 6 months prior to eligibility confirmation by the physician-investigator
- New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to eligibility confirmation by the physician-investigator.
- Serious and inadequately controlled cardiac arrhythmia
- 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 locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 1 Study of EGFRvIII-Directed CAR T Cells Combined With PD-1 Inhibition in Patients With Newly Diagnosed, MGMT-Unmethylated Glioblastoma
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.
- Conditions
- Glioblastoma
- Being tested
- CART-EGFRvIII T cells, Pembrolizumab
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART-EGFRvIII T cellsBiological
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.
PembrolizumabBiological
Also called Keytruda
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.
| Study group | Role | What they receive |
|---|---|---|
| CART-EGFRvIII + Pembrolizumab | Experimental | Not described Receives: Biological: CART-EGFRvIII T cells; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with treatment-related adverse events, using NCI CTCAE v5.0.
Measured: 15 Years
Secondary outcomes (3)
Overall survival Rate
Number of days from the date of the first CART-EGFRvIII infusion to the date of death of any cause. The survival function of OS will be calculated by the Kaplan-Meier method.
Measured: 15 Years
Progression-free survival (PFS)
The number of days from the date of the first CART-EGFRvIII infusion to the first documented disease progression (based on standard MRI evaluation using the modified RANO criteria) or date of death, whichever occurs first. PFS will be calculated by the Kaplan-Meier method.
Measured: 15 Years
Objective response rate (ORR)
The proportion of patients with complete response (CR) or partial response (PR) out of the total number of efficacy evaluable subjects. Exact 90%confidence interval for ORR will be computed.
Measured: 15 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2018
- Study start11 Mar 2019
- Primary completion27 Feb 2021
- Study completion27 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Donald O'Rourke, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03726515
- Sponsor's protocol ID
- 831706, UPCC 13318
- Status last verified
- Mar 2021
- First submitted
- 26 Oct 2018
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of EGFRvIII-Directed CAR T Cells Combined With PD-1 Inhibition in Patients With Newly Diagnosed, MGMT-Unmethylated Glioblastoma
- ClinicalTrials.gov ID
- NCT03726515
- Acronym / sponsor ID
- 831706, UPCC 13318
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 11 Mar 2019 (actual)
- Primary completion
- 27 Feb 2021 (actual)
- Study completion
- 27 Feb 2021 (actual)
- First posted
- 31 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CART-EGFRvIII + Pembrolizumab | Experimental | Biological: CART-EGFRvIII T cells, Biological: Pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- One of the following diagnoses of GBM:
- Undergone tumor resection.
- 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.
- 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).
- 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.
Key exclusion criteria (17 listed)
- Pregnant or lactating women
- Inadequate venous access for or contraindications to leukapheresis.
- Active Hepatitis B, hepatitis C, or HIV infection, or other active, uncontrolled infection
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CART-EGFRvIII T cellsautologous 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 | CART-EGFRvIII + Pembrolizumab |
| PembrolizumabAlso: Keytrudahumanized 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. | Biological | CART-EGFRvIII + Pembrolizumab |
Primary outcome
Number of subjects with treatment-related adverse events, using NCI CTCAE v5.0.
Time frame: 15 Years
3 secondary outcomes
Overall survival Rate
Time frame: 15 Years
Progression-free survival (PFS)
Time frame: 15 Years
Objective response rate (ORR)
Time frame: 15 Years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald O'Rourke, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CART-EGFRvIII T cells and Pembrolizumab in people with Glioblastoma, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with treatment-related adverse events, using NCI CTCAE v5.0. (time frame: 15 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.