89Zr-olaratumab Dosimetry in Participants With Soft Tissue Sarcoma

NCT06537596 | Recruiting Phase 1 DMC

• 1 other identifier: 89Zr-TLX300-101
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Soft Tissue Sarcoma (STS) is a type of cancer that develops in soft tissues such as muscles, tendons, fat, blood vessels, and nerves. STSs generally express a protein called Platelet-Derived Growth Factor Receptor (PDGFR)α, which makes them a target for the development of STS therapies, such as olaratumab. Olaratumab has been identified as a promising candidate to which radioactive substances can be attached for imaging or therapeutic purposes. Thus, this first in human imaging trial aims to study olaratumab combined with a radioactive metal called zirconium-89 (89Zr-TLX300-CDx) as a potential new product that may be used for STS imaging and identification of patients that may benefit from future treatments targeting PDGFRα.

Conditions

Soft Tissue Sarcoma

Keywords

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (4)

• Evaluate clinical safety and tolerability of 89Zr-TLX300-CDx

  Number of Adverse events (AEs)

  30 days

• Biodistribution of 89Zr-TLX300-CDx

  Measurement of absorbed radiation doses to organs.

  6 days

• Radiation dosimetry of 89Zr-TLX300-CDx

  Measurement of absorbed radiation doses to tumour(s) and whole body.

  6 days

• Pharmacokinetics (PK)

  Measure the antibody concentration at each timepoint to determine a PK curve.

  6 days

Secondary Outcomes (1)

• Determine a suitable antibody mass for administration

  6 days

Other Outcomes (2)

• Evaluate the correlation between tumour uptake of 89Zr-TLX300-CDx and PDGFRα expression

  30 days

• Compare the tumour uptake and detection of lesions between 89Zr-TLX300-CDx and standard of care imaging

  30 days

Study Arms (3)

Part A

EXPERIMENTAL

One Injection of 89Zr-TLX300-CDx

Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx)

Part B

EXPERIMENTAL

One Injection of 89Zr-TLX300-CDx

Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx)

Part C

EXPERIMENTAL

One Injection of 89Zr-TLX300-CDx

Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx)

Interventions

89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx) DRUG

Single administration of 89Zr-TLX300-CDx

Part A; Part B; Part C

Eligibility Criteria

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

You may qualify if:

• ≥18 years of age at the time of signing the informed consent.
• Histologically confirmed diagnosis of soft tissue sarcoma (STS)
• At least one mass of \> 2 cm in largest diameter seen on standard of care imaging (CT, MRI and/or FDG-PET).
• For Part A: Participants must have tumour PDGFRα expression confirmed by IHC. Participants must have consented to provide archived FFPE tumour tissue or be subject to a biopsy of the target tumour (if archived tissue is unavailable).
• For Parts B and C: all participants will be included regardless of their PDGFRα expression status on archival tissue/biopsy (unless otherwise specified). Participants must have consented to provide available archived FFPE tumour tissue.
• Adequate haematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500/ μL, haemoglobin ≥ 9.0 g/dL, and a platelet count of 100,000/μL obtained.
• Adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN).
• Adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the participant's creatinine clearance is ≥ 45 mL/min.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Life expectancy of at least 6 months.
• Female participants of childbearing potential must have negative pregnancy tests at screening, as well as confirmation of negative pregnancy test result within 24 hours prior to receiving 89Zr-TLX300-CDx. Female participants of childbearing potential or male participants with female partners of childbearing potential must:
• be willing to practice full and true sexual abstinence; or
• be surgically/permanently sterile or with a history of hysterectomy for women; or
• be willing to practice highly effective contraception by using: a non-oral, injected or implanted non-oestrogen progesterone based hormonal method, male condom, vaginal diaphragm, cervical cap, intrauterine device, for 3 months after the administration of 89Zr-TLX300-CDx.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Known or suspected hypersensitivity to olaratumab, DFOsq, 89Zr or any of the excipients.
• IgE antibodies against galactose-α-1,3-galactose (α-Gal) above the upper limit of normal, \> 0.7 kU/L.
• Exposure to any experimental diagnostic or therapeutic drug within 30 days from the date of planned administration of 89Zr-TLX300-CDx.
• Surgery ≤ 2 weeks prior to the administration of 89Zr-TLX300-CDx or significant ongoing complications of surgery. Biopsy ≤ 2 weeks prior to the administration of 89Zr-TLX300-CDx is allowed.
• Exposure to any radiopharmaceutical within 10 half-lives prior to the administration of 89Zr-TLX300-CDx.
• Ongoing toxicity Grade 2 or higher from previous standard or investigational therapies (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5).
• Planned to commence systemic antineoplastic therapies, immunotherapy, targeted therapy, radiotherapy and/or surgery for the period between administration of 89Zr-TLX300-CDx and last imaging timepoint.
• Serious non-malignant disease (e.g., psychiatric, infectious, autoimmune or metabolic) or any disease that may interfere with the objectives of the study or with the safety or compliance of the participant, as judged by the Investigator.
• Pregnant or lactating women.
• Participants unable to declare meaningful informed consent on their own (e.g., with legal guardian for mental disorders) or unable to tolerate the study procedures.

Sponsors & Collaborators

• Telix Pharmaceuticals (Innovations) Pty Ltd: lead

Study Sites (1)

Precision Molecular Imaging & Theranostics Pty Ltd

Melbourne, Victoria, 3051, Australia

RECRUITING

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Brenda Cerqueira, M.Sc

CONTACT

+61 83180090; brenda.cerqueira@telixpharma.com

Vanessa Penna, Ph.D

CONTACT

+61 3 9093 3880; vanessa.penna@telixpharma.com

Study Design

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

Model Details: Proof-of-concept tumour targeting of 89Zr-TLX300-CDx (Part A), assessment of 89Zr-TLX300-CDx biodistribution and tumour uptake (Part B) and radiation dosimetry (Part C).

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: August 5, 2024
• Study Start: October 31, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 19, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)