64Cu-TLX592 Phase I Safety, PK, Biodistribution and Dosimetry Study (CUPID Study)

NCT04726033 | Completed Early Phase 1

• 1 other identifier: 64Cu-TLX592-001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1 trial of TLX592, a humanised, engineered monoclonal antibody HuX592r conjugated with a DOTA chelator and radiolabelled with 64Cu (64Cu-TLX592). TLX592 is being developed as a PSMA-targeting antibody to be radiolabelled with a therapeutic radiosotope for the treatment of PSMA-expressing tumours, therefore this study has been designed to assess the safety and tolerability, pharmacokinetics, whole body biodistribution and radiation dosimetry of 64Cu-TLX592.

Conditions

Metastatic Prostate Cancer

Keywords

prostate cancer; biodistribution; 64Cu-TLX592; pharmacokinetics; dosimetery; safety

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  Treatment emergent adverse events (TEAE) will be classified according to MedDRA (Medical Dictionary for Regulatory Activities), frequency, severity according to NCI CTCAE V5.0, seriousness, and relationship of study treatment will be assessed. Laboratory abnormalities will be assessed according to the NCI CTCAE v.5.0

  Day 1 to 28

• Pharmacokinetics of 64Cu-TLX592

  Patient plasma samples at 0h, 1h, 4 ± 0.5h, 20 ± 4h and 48 ± 4h after the administration of 64Cu-TLX592 will be counted for radioactivity.

  Day 1-4 after a single administration of 64Cu-TLX592

• Biodistribution of 64Cu-TLX592

  On Days 0, Day 1 and potentially at 36-120h after administration of the investigational product, the biodistribution and tumour imaging will be performed. An end of study visit will be conducted on Day 28 ± 2 days. 64Cu-TLX592 images will be centrally analysed for absorbed organ and whole body doses in a standardised fashion. In addition, tumour absorbed doses will be determined for scientific purposes (estimation of achievable tumour doses of therapeutic nuclides labelled to TLX592)

  Up to 24h after a single administration of 64Cu-TLX592

• Dosimetry of 64Cu-TLX592

  For dosimetry analysis, biodistribution whole body PET/CT imaging will be performed at 1h, 4 ± 0.5h, 20 ± 4h, with the option for a an additional two scans to be performed between the 36-120 hours.

  Up to 5 days after a single administration of 64Cu-TLX592

Secondary Outcomes (2)

• Optimal antibody dose of TLX592

  Single diagnostic administration 1 day, followed by a diagnostic scan on Day 1

• Comparison of PSMA-targeting of different PMSA-imaging agents

  Single diagnostic administration 1 day, followed by a diagnostic scan on Day 1.

Study Arms (4)

Dose level 1 of 64Cu-TLX592

EXPERIMENTAL

Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu

Drug: 64Cu-DOTA-TLX592

Dose level 2 of 64Cu-TLX592

EXPERIMENTAL

Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 8mg of unlabelled TLX592 (mass dose of 10mg).

Drug: 64Cu-DOTA-TLX592

Dose level 3 of 64Cu-TLX592

EXPERIMENTAL

Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 18mg of unlabelled TLX592 (mass dose of 20mg).

Drug: 64Cu-DOTA-TLX592

Confirmation of optimal 64Cu-TLX592 dose

EXPERIMENTAL

Based on the result of Groups 1-3, the optimal dose and imaging timepoints will be selected to treat 3 patients with higher tumour burden (≥10 metastatic sites and/or visceral disease as detected on a 68Ga-PSMA-11 or 18F-DCFPyl PSMA PET/CT scan). Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 0, 8 or 18mg of unlabelled TLX592.

Drug: 64Cu-DOTA-TLX592

Interventions

64Cu-DOTA-TLX592 DRUG

TLX592, a humanised, engineered monoclonal antibody HuX592r conjugated with a DOTA chelator and radiolabelled with 64Cu (64Cu-TLX592)

Also known as: 64Cu-TLX592

Confirmation of optimal 64Cu-TLX592 dose; Dose level 1 of 64Cu-TLX592; Dose level 2 of 64Cu-TLX592; Dose level 3 of 64Cu-TLX592

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Biochemically recurrent metastatic adenocarcinoma of the prostate, or metastatic primary adenocarcinoma of the prostate.
• Histologically or cytologically confirmed diagnosis of adenocarcinoma of prostate.
• PSMA-expressing prostate adenocarcinoma as seen on 68Ga-PSMA-11 or 18F- DCFPyl PSMA PET/CT scanning within the last 1 month showing PSMA-avid disease.
• ECOG performance status of 0 - 1.
• Normal organ function and marrow reserve:
• White blood cell (WBC) count ≥ 2.5 x 109/L or absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
• Platelets ≥ 100 x 109/L.
• Haemoglobin ≥ 90g/L.
• Bilirubin \< 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5 - 2x ULN, must have a normal conjugated bilirubin).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.0 x ULN (or
• x ULN in the presence of liver metastases).
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min.

You may not qualify if:

• A patient is excluded from participation in the trial if one or more of the following criteria are met:
• Known active brain metastases.
• Serious active infection (as assessed by investigator).
• Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or haematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study.
• Known or suspected allergies, hypersensitivity, or intolerance to the IMP or its excipients.
• Other investigational agents within 4 weeks of randomization.
• Radiotherapy or immunotherapy within 4 weeks prior to the planned administration of 64Cu-TLX592 or continuing adverse effects (\> grade 1) from such therapy \[Common Terminology Criteria for Adverse Events (CTCAE) version 5\].
• Previous administration of any radionucleotide within 10 half-lives of 64Cu.
• Inability to understand, or unwilling to sign, a written informed consent document or to follow investigational procedures in the opinion of the investigator.
• Patients who are unable to maintain self-care.

Sponsors & Collaborators

• Telix Pharmaceuticals (Innovations) Pty Limited: lead

Study Sites (2)

Envision Medical Imaging

Perth, Western Australia, 6014, Australia

Location

GenesisCare Wembly

Perth, Western Australia, 6014, Australia

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study will consist of four groups with the initial three groups undergoing dose escalation and the fourth group will be to confirm the optimal dose and imaging conditions.

Study Record Dates

• First Submitted: October 14, 2020
• First Posted: January 27, 2021
• Study Start: August 4, 2021
• Primary Completion: December 30, 2023
• Study Completion: January 29, 2024
• Last Updated: May 1, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)