Clinical trial NCT06537596: 89Zr-olaratumab Dosimetry in Participants With Soft Tissue Sarcoma
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Soft Tissue Sarcoma
Keywords: Soft Tissue Sarcoma
Lead sponsor: Telix Pharmaceuticals (Innovations) Pty Limited
Sponsor class: INDUSTRY
First posted: 2024-08-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Proof-of-concept tumour targeting of 89Zr-TLX300-CDx (Part A), assessment of 89Zr-TLX300-CDx biodistribution and tumour uptake (Part B) and radiation dosimetry (Part C).
Primary purpose: DIAGNOSTIC

Brief 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate clinical safety and tolerability of 89Zr-TLX300-CDx
timeFrame: 30 days
measure: Biodistribution of 89Zr-TLX300-CDx
timeFrame: 6 days
measure: Radiation dosimetry of 89Zr-TLX300-CDx
timeFrame: 6 days
measure: Pharmacokinetics (PK)
timeFrame: 6 days
Secondary outcomes:
measure: Determine a suitable antibody mass for administration
timeFrame: 6 days
Other outcomes:
measure: Evaluate the correlation between tumour uptake of 89Zr-TLX300-CDx and PDGFRα expression
timeFrame: 30 days
measure: Compare the tumour uptake and detection of lesions between 89Zr-TLX300-CDx and standard of care imaging
timeFrame: 30 days
Locations:
city: Melbourne
country: Australia
facility: Precision Molecular Imaging & Theranostics Pty Ltd
state: Victoria
Study officials:
References: