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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
50
Single administration of 89Zr-TLX300-CDx
Princess Alexandra Hospital 199 Ipswich Road, Woolloongabba
Brisbane, Queensland, Australia
RECRUITINGPrecision Molecular Imaging & Theranostics Pty Ltd
Melbourne, Victoria, Australia
RECRUITINGGenesisCare Murdoch 100 Murdoch Drive, Murdoch WA
Perth, Western Australia, Australia
NOT_YET_RECRUITINGEvaluate clinical safety and tolerability of 89Zr-TLX300-CDx
Number of Adverse events (AEs)
Time frame: 30 days
Biodistribution of 89Zr-TLX300-CDx
Measurement of absorbed radiation doses to organs.
Time frame: 6 days
Radiation dosimetry of 89Zr-TLX300-CDx
Measurement of absorbed radiation doses to tumour(s) and whole body.
Time frame: 6 days
Pharmacokinetics (PK)
Measure the antibody concentration at each timepoint to determine a PK curve.
Time frame: 6 days
Determine a suitable antibody mass for administration
SUV values of tumour lesions and tumour to background organ (e.g. blood/liver/muscle) ratios.
Time frame: 6 days
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