Clinical Trials /

CART-EGFRvIII + Pembrolizumab in GBM

NCT03726515

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CART-EGFRvIII + Pembrolizumab in GBM
  • Official Title: Phase 1 Study of EGFRvIII-Directed CAR T Cells Combined With PD-1 Inhibition in Patients With Newly Diagnosed, MGMT-Unmethylated Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: 831706, UPCC 13318
  • NCT ID: NCT03726515

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
CART-EGFRvIII T cellsCART-EGFRvIII + Pembrolizumab
PembrolizumabKeytrudaCART-EGFRvIII + Pembrolizumab

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.

Trial Arms

NameTypeDescriptionInterventions
CART-EGFRvIII + PembrolizumabExperimental
  • CART-EGFRvIII T cells
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          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.

        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

         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
                  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.

        12. Patients with tumors primarily localized to the brain stem or spinal cord.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with treatment-related adverse events, using NCI CTCAE v5.0.
Time Frame:5 Months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival Rate
Time Frame:15 Years
Safety Issue:
Description: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.
Measure:Progression-free survival (PFS)
Time Frame:15 Years
Safety Issue:
Description: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.
Measure:Objective response rate (ORR)
Time Frame:15 Years
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

January 7, 2020