This is an open-label, first-in-human, exploratory Phase 0 study evaluating the safety and diagnostic imaging performance of the DOTA-STR-17126 theranostic pair in patients with advanced or metastatic breast or prostate cancer. The study investigates \[68Ga\]Ga-DOTA-STR-17126 for PET imaging and, in patients with positive GRPR uptake, a low dose of \[177Lu\]Lu-DOTA-STR-17126 for SPECT imaging and dosimetry.
The primary objective is to assess safety and tolerability. Secondary objectives include evaluation of imaging quality, biodistribution, pharmacokinetics, and radiation dosimetry. Exploratory objectives assess correlations between GRPR expression in tumour tissue and imaging uptake.
The study is conducted at a single centre in Australia, with 12 evaluable participants (up to 20 enrolled), and supports the development of a GRPR-targeted theranostic approach for personalised cancer management.
Ability to understand and willingness to provide informed consent
Adults ≥ 18 years of age
Must have the following histologically or cytologically confirmed diagnosis of advanced or metastatic i. breast cancer ii. prostate cancer
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
Known hypersensitivity to the investigational medicinal products (DOTA-STR-17126) or any of the excipients.
Participants with Class 3 or 4 New York Heart Association (NYHA) Congestive Heart Failure.
Average QTc (using the Fridericia correction calculation) > 470 msec for females and QTcF >450 msec for males on screening ECG or history of congenital long QT syndrome.
Clinically significant bleeding within two weeks prior to trial entry (i.e., gastrointestinal bleeding, intracranial bleeding).
Single group
[177Lu]Lu-DOTA-STR-17126
DrugParticipants will receive a low dose of \[177Lu\]Lu-DOTA-STR-17126, dose activity: 1.0+/-0.5 GBq (50 micrograms peptide) of \[177Lu\]Lu-DOTA-STR-17126 precursor will be administered as a slow infusion.
[68Ga]Ga-DOTA-STR-17126
DrugParticipants will receive a single intravenous bolus dose of 150+/-50MBq (25 - 50 micrograms) of \[68Ga\]Ga-DOTA-STR-17126 precursor.
Number of participants with adverse events (AEs), serious adverse events (SAEs), with abnormal laboratory parameters (hematology, blood chemistry, and urinalysis), abnormal Physical examinations findings
1\. To evaluate adverse events (AEs) and serious adverse events (SAEs) by means of Common Toxicity Criteria Adverse Events (CTCAE version 5.0 Nov 2017); Assess occurrence and severity of AEs and SAEs; Monitor safety laboratory parameters (haematology, blood chemistry, and urinalysis) before, during and after IMP injections. The Common Terminology Criteria for Adverse Events (CTCAE) is a standardized, 1-5 severity grading system for classifying cancer treatment side effects (adverse events). Grades range from mild (1) to death (5). It is widely used in oncology to determine treatment safety, drug dosage modifications, and to document clinical trial toxicity
Standardized Uptake Value (SUV) of [⁶⁸Ga]Ga-DOTA-STR-17126
Calculation of Standardized Uptake Value (SUV) (max, mean, peak) \* between tumour and suitable reference organs (using liver parenchyma, lung parenchyma and mediastinal blood pool as reference regions) by PET/CT imaging, Higher numbers e.g., above 2.5 often highly suggestive of malignancy (cancerous growth. Lower numbers e.g., below 2.5 frequently indicate benign (non-cancerous) growths. SUVmax vs. SUVmean: A scan report will usually specify SUV\_max as the highest, most active single point in the tumor or SUV\_mean (the average activity across the entire tumor.
PET/CT image quality of [⁶⁸Ga]Ga-DOTA-STR-17126
Qualitative assessment of PET/CT image quality using a 5-point scale from excellent to poor image, with parameters such as intensity, sharpness, noise of tumour uptake related to reference regions.
Tumour to Background Ratio (TBR) of [⁶⁸Ga]Ga-DOTA-STR-17126
The ability to confirm preferential accumulation of \[68Ga\] Ga-DOTA-STR-17126 in target lesions and comparable detectability of tumour lesions by PET/CT, taking also into account the extent of uptake in non-target normal organs, and establish intra-participant image quality protocol. • Tumour to Background Ratio (TBR). High TBR: Indicates a "hot" or very active tumor that is easy to distinguish from the surrounding healthy tissue (e.g., a TBR of 3.0 or higher). Low TBR: Indicates that the tumor looks very similar to the surrounding background tissue, which can make it difficult to identify or measure accurately.
Concentration of [68Ga]Ga-DOTA-STR-17126 and [177Lu]Lu-DOTA-STR-17126
Calculate concentration of \[68Ga\]Ga-DOTA-STR-17126 and of \[177Lu\]Lu-DOTA-STR-17126 in blood by counting radioactivity in respective samples at specific time intervals (radio-PK)
Number of tumour lesions within tumour tissue sample that are positive for GRPR expression based on immunohistochemistry (IHC)
To calculate the number of tumour lesions within tumour tissue sample that are positive for GRPR expression based on immunohistochemistry (IHC) or quantitative polymerase chain reaction (qPCR), protein and RNA, respectively
Staining intensity (% of positive cells and intensity) in tumour tissue
To compare staining intensity (% of positive cells and intensity) in tumour tissue samples to SUVmax uptake in un-matched PET imaging scans
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