Phase 1 Open-label Study of 123I-ATT001 in Subjects With Relapsed Glioblastoma

NCT06650605 | Completed Phase 1 DMC

• 2 other identifiers: PIL1011006521
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Glioma Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (2)

• Part 1 - Dose Escalation: Frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

  To assess safety and tolerability of 123I-ATT001

  Screening to end of treatment visit (28 days after last dose of 123I-ATT001)

• Part 1- Dose Escalation: Incidence of Dose Limiting Toxicity (DLT)

  Evaluated by monitoring of Adverse Events.

  Day 1 to Day 14 of 123I-ATT001 administration

Secondary Outcomes (6)

• Part 1 - Dose Escalation: biodistribution and pharmacokinetics of 123I-ATT001 in blood

  Collected 1 hour, 4 hours and 24 hours post each dose and optionally at 48 hours post first dose.

• Part 1- Dose Escalation: biodistribution and pharmacokinetics of 123I-ATT001 in urine.

  Collected 24 hours post first dose

• Part 1 - Dose Escalation: radiation dosimetry of 123I-ATT001 (exposure of each organ to radiation)

  1 and 4 and 24 hours post first dose and 4 hours post fourth dose.

• Part 1- Dose Escalation: preliminary assessment of the antitumour activity of 123I-ATT001

  Screening, Day 14 post each dose, 28 days after last dose, then a further 3 times every 8 weeks at follow up.

• Part 1 - Dose Escalation: effect of 123I-ATT001 on neurological function

  Screening, the day of the 1st, 3rd and 5th (if given) dose, may also be performed within 48 hours prior to dose administration. It will also be performed on the End of Treatment visit which takes place 28 days post last dose.

Study Arms (1)

Part 1 Dose Escalation & Dose Expansion

EXPERIMENTAL

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

Drug: 123I-ATT001

Interventions

123I-ATT001 DRUG

123I-ATT001

Part 1 Dose Escalation & Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• written informed consent
• Men and women over 18 years of age.
• 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.
• 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.
• Eastern Cooperative Oncology Group Performance status of 0 or 1.
• Adequate organ function
• 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.
• Be able to understand and comply with the requirements of the study, as judged by the Investigator.

You may not qualify if:

• 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.
• 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.
• Prior anticancer treatments within the following time periods:
• Chemotherapy within 4 weeks of enrolment or 5 half-lives, whichever is shorter.
• Targeted small molecule therapy within 4 weeks of enrolment or 5 half-lives, whichever is shorter.
• Immunotherapy (including monoclonal antibody therapy) or radiation therapy within 4 weeks prior to study day 1.
• Unresolved NCI-CTCAE grade 2 or higher toxicity (except stable neurological toxicities/deficits related to disease process, alopecia).
• Patients with a known allergy to Olaparib or Iodine.
• 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.
• Any condition that precludes the proper performance of SPECT and/or MRI scan
• 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.
• 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).
• Psychiatric, substance misuse or functional disorders that prevent subjects from providing informed consent, following protocol instructions or cooperating with the requirements of the study.
• Active infection requiring systemic therapy.
• 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.

Sponsors & Collaborators

• Theragnostics Ltd: lead

Study Sites (2)

University College London Hosptial

London, United Kingdom

Location

University Hospital Southampton

Southampton, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Paul Mulholland

  University College London Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: October 21, 2024
• Study Start: July 4, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)