A Phase I, Open Label, First-In-Humans (FIH), Single Dose Level Study to Evaluate the Safety, Tolerability, Immunogenicity and Preliminary Efficacy of ITI-1001 In Patients with Newly Diagnosed Glioblastoma (GBM)

ENROLLING
Protocol # :
22-587
Conditions
Glioblastoma
Phase
I
Disease Sites
Brain and Nervous System
Principal Investigator
Reardon, David, A.

Trial Description

This Phase I clinical trial will evaluate the safety, tolerability, immunogenicity, and
preliminary efficacy of 8 mg ITI-1001 in participants with newly diagnosed glioblastoma
(GBM).

Eligibility Requirements

Inclusion Criteria:

1. Newly diagnosed patients with histopathological diagnosis of WHO grade IV glioma
(GBM).

2. Age ≥ 18 years.

3. Patient must have undergone a gross/near-gross total surgical resection of tumor by
analysis of residual enhancing tumor remnant on the immediate post-operative MRI
(within 72 hours after surgery) as defined by ≤ 3 cm2 residual enhancing tumor longest
perpendicular planes by MRI.

4. Planned standard adjuvant chemoradiation (SOC RT + TMZ for 6 weeks).

5. Karnofsky performance status ≥ 70.

6. Life expectancy ≥ 3 months.

7. All patients must be able to understand and be willing to sign written informed
consent and aware of the investigational nature of the study.

8. Patient has adequate renal function (creatinine ≤ 1.5 times the upper limit of normal
[ULN]) or a glomerular filtration rate (GFR) of ≥ 50 mL/min/1.73 m2).

9. Patient has adequate hepatic function, as evidenced by a total bilirubin ≤1.5 times
the ULN, aspartate transaminase (AST), and /or alanine transaminase (ALT) ≤3 times the
ULN.

10. Patient has adequate bone marrow function, as evidenced by hemoglobin ≥ 9.0 g/dL in
the absence of transfusion within the 72 hours prior to the screening visit, platelet
count ≥ 100×109cells/L, and absolute neutrophil count (ANC) ≥ 1.5×109 cells/L.

11. Patient and his/her partner agree to use adequate contraception after providing
written informed consent through 3 months after the last investigational product dose,
as follows:

- For women: Negative pregnancy test during screening and at baseline and compliant
with 2 methods of medically approved contraceptive regimens during and for 3
months after the treatment period or documented to be surgically sterile or
postmenopausal.

- For men: Compliant with 2 methods of medically approved contraceptive regimens
during and for 3 months after the treatment period or documented to be surgically
sterile.

12. Patient is willing to participate in the study and comply with all study requirements.

Exclusion Criteria:

1. Participation in another therapeutic clinical trial.

2. Implantable electronic device.

3. Pregnant or breast feeding.

4. Tumor location or tumor primarily located in spinal cord or brain stem, multi-focal
disease, or significant leptomeningeal disease.

5. Evidence of significantly increased intracranial pressure (midline shift > 5mm,
clinically significant papilledema, vomiting and nausea or reduced level of
consciousness).

6. Known history of AIDS/HIV. Testing is not required.

7. Patient has a history of other malignancy treated with curative intent within the
previous 3 years with the exception of adequately treated non-melanoma skin cancer or
carcinoma in situ of the cervix. Patients with previous invasive cancers are eligible
if the treatment was completed more than 3 years prior to initiating current study
treatment, and there is no evidence of recurrent disease.

8. Patient has an important medical illness or abnormal laboratory finding that, in the
Investigator's opinion, would increase the risk of participating in this study.

9. History of unstable cardiac arrhythmia or palpitations [e.g., supraventricular
tachycardia, atrial fibrillation, frequent ectopy, or sinus bradycardia (i.e., <50
beats per minute on exam)] prior to study entry. Sinus arrhythmia is not excluded.

10. Any chronic or active neurologic disorder that in the opinion of the Investigator
would compromise the patient participation and/or integrity of the study. Patients
with seizures due to recent onset of GBM that are medically controlled are eligible.

11. Syncopal episode within 12 months of screening.

12. Presence of any surgical or traumatic metal implants at the site of administration
(medial deltoid or vastus lateralis muscles or overlying skin) or conditions
incompatible with electroporation per instruction manual of the TriGrid TDS-IM V2.

13. Patients requiring dexamethasone within 7 days before first priming vaccination of
ITI-1001.

14. Contraindication to IM injections or blood draws.

15. Less than 2 acceptable potential injection sites for IM injection and electroporation
considering the left and right medial deltoid, and anterolateral quadriceps muscles. A
site for injection and electroporation is not acceptable if there is inadequate muscle
mass to support at least a 19 mm/0.75 inch injection depth or a skinfold thickness
measurement of ≥50 mm/1.97 inch as assessed using the provided caliper. Eligible
injection sites must also be free from tattoos, hypertrophic skin patches, keloids or
other skin conditions which could interfere with the administration procedure or
subsequent assessment of local reactogenicity.

Note: To ensure adequate muscle mass for administrations, for participants with a
weight ≤65 kg, potentially eligible administration sites are confined to the outer
aspect of the upper thigh (left or right vastus lateralis muscle) (i.e,, the left and
right medial deltoid are not eligible administration sites).

16. Any condition that, in the Investigator's opinion, would render the patient unable to
comply with the study procedures and requirements.

22-587