89Zr-olaratumab Dosimetry in Participants With PDGFR Alpha Positive Solid Tumours and Soft Tissue Sarcoma
Soft Tissue Sarcoma (STS) is a cancer of soft tissues that often expresses Platelet-Derived Growth Factor Receptor (PDGFR)α, a potential therapeutic target. PDGFRα is also found in other advanced solid tumours. Olaratumab, a PDGFRα-targeted antibody, may be used to deliver radioactive isotopes for imaging or therapy.
This first-in-human study will evaluate zirconium-89-labelled olaratumab (⁸⁹Zr-TLX300-CDx) for imaging in patients with STS, selected PDGFRα-positive solid tumours and identification of patients that may benefit from future treatments.
Study details:
Platelet-derived growth factor receptor α (PDGFRα) is expressed in soft tissue sarcoma (STS) and other solid tumours, where it may serve as a therapeutic target. Olaratumab is a PDGFRα-targeted antibody with potential to act as a targeting moiety for both imaging and therapeutic radioisotopes. Its favourable safety profile and ability to bind and be internalised by PDGFRα-expressing tumour cells make it a promising radionuclide targeting agent.
⁸⁹Zr-TLX300-CDx is being developed for PDGFRα PET imaging in STS and selected PDGFRα-positive solid tumours. The aim of this study is to demonstrate tumour targeting of ⁸⁹Zr-TLX300-CDx and assess its safety and radiation dosimetry, to support future development of olaratumab as a radiopharmaceutical. SCHEDULE OF ASSESSMENTS.
Part A. IMAGING:. 1 single injection of 89Zr-TLX300-CDx on Day 1 followed by whole-body imaging at 4h ± 0.
5h and Day 6 ± 1 post-injection. OPTIONAL:. Imaging at Day 4 ± 1 post-injection.
Blood Collection for Pharmacokinectics:. Pre-injection, 4h ± 0. 5h and 6 days ± 1 day post-injection.
OPTIONAL:. Blood collection at Day 4 ± 1 post-injection. Part B.
IMAGING:. 1 single injection of 89Zr-TLX300-CDx on Day 1 followed by whole-body imaging at Day 6 ± 1 post-injection. OPTIONAL:.
Imaging at 4h ± 0. 5h post-injection and at Day 4 ± 1 post-injection. Blood Collection for Pharmacokinectics:.
Pre-injection, 4h ± 0. 5h and 6 days ± 1 day post-injection. OPTIONAL:.
Blood collection at Day 4 ± 1 post-injection. Part C:. IMAGING:.
1 single injection of 89Zr-TLX300-CDx on Day 1 followed by whole-body imaging at 24h ± 4h, 4 days ± 1 post-injection and 7 days ± 1 day post-injection. OPTIONAL:. Dynamic imaging 15 min ± 2 min post-injection at selected sites (extended field-of-view scanner available) and static imaging at 4h ± 0.
5h post-injection. Blood Collection for Pharmacokinectics:. Pre-injection, 4h ± 0.
5h, 24h ± 4h, 4 days ± 1 day and 7 days ± 1 day post-injection.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- ≥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: 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.
- 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
- 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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
DIAGNOSTIC
Phase
- PHASE1
Study ID
NCT06537596
Intervention or treatment
DRUG: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx)
Conditions
- Soft Tissue Sarcoma
- PDGFR Alpha Positive Solid Tumours
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Research sites nearby
Closest Location:
Precision Molecular Imaging & Theranostics Pty Ltd
Select from list below to view details:
Precision Molecular Imaging & Theranostics Pty Ltd
Melbourne, Victoria, Australia
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Who is running the clinical trial?
Telix Pharmaceuticals (Innovations) Pty Ltd
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Part A
| Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx) |
EXPERIMENTAL: Part B
| Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx) |
EXPERIMENTAL: Part C
| Drug: 89Zr-DFOsq-olaratumab (89Zr-TLX300-CDx) |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 Outcome
| 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 |
References
Clinical Trials Gov: 89Zr-olaratumab Dosimetry in Participants With PDGFR Alpha Positive Solid Tumours and Soft Tissue SarcomaOther trials to consider
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