89Zr-olaratumab Dosimetry in Participants With Soft Tissue Sarcoma (ZOLAR)

An Open-label, Phase 1 Study to Assess Safety, Tolerability, Dosimetry, Pharmacokinetics and Imaging Properties of 89Zr-olaratumab (89Zr-TLX300-CDx) in Participants With Soft Tissue Sarcoma.

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.

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx)

Detailed Description

Platelet-derived growth factor receptor α (PDGFRα) is expressed on soft tissue sarcoma (STS) where it could act as a potential therapeutic target. Olaratumab is a PDGFRα-targeted antibody that has the potential to act as the targeting moiety for both imaging and therapeutic radioisotopes. Olaratumab's demonstrated safety profile and its ability to target PDGFRα on STS cell surfaces and be rapidly internalised, make it a promising candidate for use as a radionuclide targeting agent in STS. 89Zr-TLX300-CDx is being developed for PDGFRα molecular imaging with positron emission tomography (PET) in STS. The aim of this study is to provide proof-of-concept tumour targeting of 89Zr-TLX300-CDx and assess the safety and radiation dosimetry of radiolabelled olaratumab. This study will inform future development of olaratumab as a therapeutic radiopharmaceutical agent in STS.

SCHEDULE OF ASSESSMENTS

Part A and B:

IMAGING:

1 single injection of 89Zr-TLX300-CDx on Day 1 and whole-body imaging at 6 days ± 1 day post-injection

Blood Collection for PHARMACOKINETICS:

Pre-injection, 4h ± 0.5h and 6 days ± 1 day post-injection.

OPTIONAL:

Imaging at 4h ± 0.5h post-injection.

Part C:

IMAGING:

1 single injection of 89Zr-TLX300-CDx on Day 1, whole-body imaging at 24h ± 4h post-injection, whole-body imaging at 4 days ± 1 post-injection and whole-body imaging at 7 days ± 1 day post-injection

Blood collection for PHARMACOKINECTCS:

Pre-injection, 4h ± 0.5h, 24h ± 4h, 4 days ± 1 day and 7 days ± 1 day post-injection.

OPTIONAL:

Dynamic imaging 15 min ± 2 min post-injection at selected sites (extended field-of-view scanner is available), imaging at 4h ± 0.5h post-injection and imaging at 7h ± 1hpost-injection

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Brenda Cerqueira, M.Sc; Phone Number: +61 83180090; Email: brenda.cerqueira@telixpharma.com
• Study Contact Backup: Name: Vanessa Penna, Ph.D; Phone Number: +61 3 9093 3880; Email: vanessa.penna@telixpharma.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3051
      • Recruiting
      • Precision Molecular Imaging & Theranostics Pty Ltd
      • Principal Investigator: Rodney Hicks, Prof.
      • Contact: Christopher Marinakis, MMedRad, BBSc; Phone Number: +61 3 94545804; Email: cmarinakis@mtic.net.au
      • Contact: Jason Callahan; Phone Number: +61 3 94545804; Email: jcallahan@mtic.net.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

1. ≥18 years of age at the time of signing the informed consent.
2. Histologically confirmed diagnosis of soft tissue sarcoma (STS)
3. At least one mass of > 2 cm in largest diameter seen on standard of care imaging (CT, MRI and/or FDG-PET).

4. 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.

5. 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.
6. 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).
7. 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.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
9. Life expectancy of at least 6 months.

10. 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:

    1. be willing to practice full and true sexual abstinence; or
    2. be surgically/permanently sterile or with a history of hysterectomy for women; or
    3. 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.
11. 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.

EXCLUSION CRITERIA:

1. Known or suspected hypersensitivity to olaratumab, DFOsq, 89Zr or any of the excipients.
2. IgE antibodies against galactose-α-1,3-galactose (α-Gal) above the upper limit of normal, > 0.7 kU/L.
3. Exposure to any experimental diagnostic or therapeutic drug within 30 days from the date of planned administration of 89Zr-TLX300-CDx.
4. 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.
5. Exposure to any radiopharmaceutical within 10 half-lives prior to the administration of 89Zr-TLX300-CDx.
6. Ongoing toxicity Grade 2 or higher from previous standard or investigational therapies (Common Terminology Criteria for Adverse Events [CTCAE] version 5).
7. 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.
8. 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.
9. Pregnant or lactating women.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; One Injection of 89Zr-TLX300-CDx	Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx); Single administration of 89Zr-TLX300-CDx
Experimental: Part B; One Injection of 89Zr-TLX300-CDx	Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx); Single administration of 89Zr-TLX300-CDx
Experimental: Part C; One Injection of 89Zr-TLX300-CDx	Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx); Single administration of 89Zr-TLX300-CDx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate clinical safety and tolerability of 89Zr-TLX300-CDx	Number of Adverse events (AEs)	30 days
Pharmacokinetics (PK)	Measure the antibody concentration at each timepoint to determine a PK curve.	6 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine a suitable antibody mass for administration	SUV values of tumour lesions and tumour to background organ (e.g. blood/liver/muscle) ratios.	6 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the tumour uptake and detection of lesions between 89Zr-TLX300-CDx and standard of care imaging	89Zr-TLX300-CDx uptake within tumours and organs and Localisation of tumour deposits on conventional imaging (CT, MRI and/or FDGPET)	30 days
Evaluate the correlation between tumour uptake of 89Zr-TLX300-CDx and PDGFRα expression	Immunohistochemistry expression of PDGFRα in tumour tissue AND SUV tumour values and tumour to background ratios.	30 days

Collaborators and Investigators

• Sponsor: Telix Pharmaceuticals (Innovations) Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: July 31, 2024
• First Posted (Actual): August 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Soft Tissue Sarcoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Antineoplastic Agents; Olaratumab
• Other Study ID Numbers: 89Zr-TLX300-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No