Phase 1 Open-label Study of 123I-ATT001 in Subjects with Relapsed Glioblastoma (CITADEL-123)

Theragnostics

Status and phase: Enrolling; Phase 1

Conditions: Glioma Glioblastoma Multiforme

Treatments: Drug: 123I-ATT001

Study type: Interventional

Funder types: Industry

Identifiers

NCT06650605

PIL101

1006521 (Other Identifier)

Details and patient eligibility

About

Phase I open-label trial of 123I-ATT001 monotherapy and in combination with treatment therapies in subjects with relapsed glioblastoma.

Full description

The main goals of this study are to understand if 123I-ATT001 is safe and tolerable to treat participants with relapsed glioblastoma and to determine the maximum tolerated dose that can be given to participants without any unacceptable side effects.

The study consists of two parts:

• Part 1 is a dose escalation study where three doses of 123I-ATT001 will be tested, starting with the lowest dose. When a recommended dose (RD) has been declared, a monotherapy expansion cohort will be open at that dose level.

In Part 1 participants will receive a 123I-ATT001 dose, once per week, for four weeks (+ two optional extra cycles).

• Part 2 is a dose expansion study where one dose of 123I-AT001 will be tested in combination with other therapies. Part 2 will begin after the Part 1 has completed and a recommended part 2 dose has been chosen.

The specific details and combination therapies for Part 2 of the study will be added via a protocol amendment at a later date.

Enrollment: 67 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. written informed consent
2. Men and women over 18 years of age.
3. Histologically confirmed recurrent glioblastoma (grade IV) as per WHO criteria 2021 (IDH- wild type only) where the subjects have an Ommaya reservoir in an intralesional cavity of at least 5 mL volume.
4. Documented recurrent disease (radiological, based on RANO v.1.0) within 3 months prior to first study drug administration with no suitable standard of care options available.
5. Eastern Cooperative Oncology Group Performance status of 0 or 1.
6. Adequate organ function
7. Women of childbearing potential must use two forms of reliable contraception before starting 123I-ATT001 treatment, during therapy and for 6 months after receiving the last dose of 123I-ATT001. All male subjects must agree to not donate sperm during the study and for 6 months after the last dose of study drug.
8. Be able to understand and comply with the requirements of the study, as judged by the Investigator.

Exclusion criteria

1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.

2. Diagnosis of immunodeficiency or receiving systemic steroid therapy of up to 4 mg/ day dexamethasone or equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.

3. Prior anticancer treatments within the following time periods:

   1. Chemotherapy within 4 weeks of enrolment or 5 half-lives, whichever is shorter.
   2. Targeted small molecule therapy within 4 weeks of enrolment or 5 half-lives, whichever is shorter.
   3. Immunotherapy (including monoclonal antibody therapy) or radiation therapy within 4 weeks prior to study day 1.

4. Unresolved NCI-CTCAE grade 2 or higher toxicity (except stable neurological toxicities/deficits related to disease process, alopecia).

5. Patients with a known allergy to Olaparib or Iodine.

6. Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.

7. Any condition that precludes the proper performance of SPECT and/or MRI scan

8. Any clinically significant abnormalities in resting ECG at the time of screening including prolonged QTcF (>450 ms for males; >470 ms for females) and cardiac arrhythmias, as judged by the Investigator or designee.

9. Unstable systemic disease (including but not limited to active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).

10. Psychiatric, substance misuse or functional disorders that prevent subjects from providing informed consent, following protocol instructions or cooperating with the requirements of the study.

11. Active infection requiring systemic therapy.

12. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 3 months after the last dose of study treatment.

13. Subject that has a condition or is in a situation, which in the Investigators opinion may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study.

14. History of non- infectious pneumonitis within the last 3 years.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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67 participants in 1 patient group

Part 1 Dose Escalation & Dose Expansion

Experimental group

Description:

Dose Escalation: 123I-ATT001 Dose Level 1 123I-ATT001 Dose Level 2 123I-ATT001 Dose Level 3 Dose Expansion: 123I-ATT001 Recommended Dose from Dose Escalation

Treatment:

Drug: 123I-ATT001