89Zr-olaratumab Dosimetry in Participants With PDGFR Alpha Positive Solid Tumours and Soft Tissue Sarcoma

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.

Inclusion criteria

• ≥18 years of age at the time of signing the informed consent.
• Histologically confirmed diagnosis of soft tissue sarcoma (STS). Patients with indications other than STS, that could be PDGFRα positive, will also be considered This would be subject to case-by-case approval by the Sponsor.
• At least one mass of > 2cm in largest diameter seen on standard care imaging (CT or MRI) or at least one lesion detected positive via FDG-PET.
• Participants must have consented to provide prior/archival FFPE tumour tissue or biopsy/resected tissues collected up to 30 days after visit 2 (89Zr-TLX300-CDx administration) - please refer to the Laboratory manual for description of tissue requirements.

It is preference that biopsies have been collected within 3 months of trial participation (but not mandatory).

• 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.
• 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.

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 ULN, >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.
• 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, i.e., (Visit 4 for Parts A and B; Visit 5 for Part C). Existing or ongoing therapies may be continued during the imaging window, without washout period.
• Serious non-malignant disease (e.g., psychiatric, infectious, autoimmune or metabolic), unresolved serious symptoms from previous therapies, 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 person.
• 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.