89Zr-olaratumab Dosimetry in Participants With Soft Tissue Sarcoma

Last updated: December 16, 2024
Sponsor: Telix Pharmaceuticals (Innovations) Pty Ltd
Overall Status: Active - Recruiting

Phase

1

Condition

Sarcoma (Pediatric)

Sarcoma

Soft Tissue Sarcoma

Treatment

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

Clinical Study ID

NCT06537596
89Zr-TLX300-101
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 besubject 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 PDGFRαexpression 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 aspartatetransaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit ofnormal (ULN).

  7. Adequate renal function as defined by serum creatinine ≤ 1.5 × the institutionalULN. If creatinine is above the ULN, the participant's creatinine clearance is ≥ 45mL/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 atscreening, as well as confirmation of negative pregnancy test result within 24 hoursprior to receiving 89Zr-TLX300-CDx. Female participants of childbearing potential ormale participants with female partners of childbearing potential must:

  11. be willing to practice full and true sexual abstinence; or

  12. be surgically/permanently sterile or with a history of hysterectomy for women;or

  13. be willing to practice highly effective contraception by using: a non-oral,injected or implanted non-oestrogen progesterone based hormonal method, malecondom, vaginal diaphragm, cervical cap, intrauterine device, for 3 monthsafter the administration of 89Zr-TLX300-CDx.

  14. Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol.

Exclusion

EXCLUSION CRITERIA:

  1. Known or suspected hypersensitivity to olaratumab, DFOsq, 89Zr or any of theexcipients.

  2. IgE antibodies against galactose-α-1,3-galactose (α-Gal) above the upper limit ofnormal, > 0.7 kU/L.

  3. Exposure to any experimental diagnostic or therapeutic drug within 30 days from thedate of planned administration of 89Zr-TLX300-CDx.

  4. Surgery ≤ 2 weeks prior to the administration of 89Zr-TLX300-CDx or significantongoing 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 administrationof 89Zr-TLX300-CDx.

  6. Ongoing toxicity Grade 2 or higher from previous standard or investigationaltherapies (Common Terminology Criteria for Adverse Events [CTCAE] version 5).

  7. Planned to commence systemic antineoplastic therapies, immunotherapy, targetedtherapy, 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 ormetabolic) or any disease that may interfere with the objectives of the study orwith 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., withlegal guardian for mental disorders) or unable to tolerate the study procedures.

Study Design

Total Participants: 50
Treatment Group(s): 1
Primary Treatment: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx)
Phase: 1
Study Start date:
October 31, 2024
Estimated Completion Date:
August 31, 2026

Study 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

Connect with a study center

  • Melbourne Theranostic Innovation Centre

    Melbourne, Victoria 3051
    Australia

    Site Not Available

  • Precision Molecular Imaging & Theranostics Pty Ltd

    Melbourne, Victoria 3051
    Australia

    Active - Recruiting

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