First-in-human Imaging Study of Theranostic Pair [68Ga]Ga-DOTA-STR-17126 and Low-dose [177Lu]Lu-DOTA-STR-17126 in Patients With Advanced or Metastatic Cancer (DOTA-STR-17126)

An Open-label, First-in-human, Exploratory Imaging Study of the DOTA-STR-17126 Theranostic Pair [68Ga]Ga-DOTA-STR-17126 and Low-dose [177Lu]Lu-DOTA-STR-17126 in Patients With Advanced or Metastatic Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer; Metastatic Breast Cancer; Metastatic Prostate Cancer; Theranostic; Active Cancer; GRPR-Targeted Molecular Imaging; Theranostic Radiopharmaceuticals; Radiopharmaceutical
• Intervention / Treatment: Drug: [177Lu]Lu-DOTA-STR-17126; Drug: [68Ga]Ga-DOTA-STR-17126

Detailed Description

This study is an open-label, first-in-human, exploratory Phase 0 clinical trial conducted at a single centre in Australia to characterise the safety profile, imaging performance, biodistribution, pharmacokinetics, and radiation dosimetry of the DOTA-STR-17126 theranostic pair in patients with advanced malignancy. The investigational approach uses a stepwise theranostic design in which all enrolled participants receive a single intravenous bolus administration of the GRPR-targeted PET radiopharmaceutical [68Ga]Ga-DOTA-STR-17126, followed by serial whole-body PET/CT imaging to evaluate tumour uptake and normal organ distribution. Participants demonstrating sufficient GRPR-positive tumour uptake on PET imaging may subsequently receive a single low-dose, slow intravenous infusion of [177Lu]Lu-DOTA-STR-17126, with serial planar and SPECT/CT imaging performed over several days to assess biodistribution and enable organ and tumour dosimetry calculations. Blood and urine samples are collected at predefined time points to support pharmacokinetic and radiation dosimetry analyses, alongside intensive clinical and laboratory safety monitoring. The study is exploratory in nature and is designed to optimise imaging protocols, generate human dosimetry data, and establish an initial safety and tolerability profile for this novel GRPR antagonist-based theranostic platform, thereby informing the design and dose selection for subsequent phase I/II clinical development.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Amma P Owusu, RN BSc MN; Phone Number: +61498120411; Email: research.iit@icon.team
• Study Contact Backup: Name: Duncan Colyer, RN BN PGDip; Email: research.iit@icon.team

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion criteria refer to the enrolment of participants for the PET/CT and SPECT/CT imaging with the radioligands; PET imaging tracer [68Ga]Ga-DOTA-STR-17126 and with the SPECT imaging tracer [177Lu]Lu-DOTA-STR-17126. Participants must meet all of the following inclusion criteria to be eligible for enrolment.

1. Ability to understand and willingness to provide informed consent
2. Adults ≥ 18 years of age
3. Must have the following histologically or cytologically confirmed diagnosis of advanced or metastatic i. breast cancer ii. prostate cancer
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
5. Participant must have clinical or radiological documented tumour progression as established by the Investigator within 30 days of signing consent for the study
6. Participants who have exhausted standard-of-care systemic therapies in their metastatic setting. At least one detectable by conventional imaging tumour lesion with any diameter of ≥ 1 cm in size

7. Participants must have adequate organ and bone marrow function, defined as follows:

   i. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 ii. Platelet count ≥ 100,000/mm3 iii. Haemoglobin ≥ 9.0 g/dL iv. AST, ALT, alkaline phosphatase ≤ 3 times upper limit of normal (ULN) if there is no evidence of liver metastases or ≤5 ULN in the presence of liver metastases v. Total bilirubin ≤ 2 times upper limit of normal (ULN) vi. Creatinine ≤ 2 times ULN and creatinine clearance (CrCL) ≥ 60mL/min using the Cockcroft Gault equation (Appendix 2)

8. Able to remain still for up to 60 minutes per scan
9. Any other condition which, in the opinion of the Investigator, would preclude participation in this study Optional: Participants that have available archival tissue (at least 15 consecutive, unstained, formalin-fixed, paraffin embedded (FFPE) slides or 1 FFPE block), or a fresh tumour biopsy sample that opt to provide samples will be used for GRPR analysis (histology staining or RNA measurements). Participants without any archival tissue or fresh biopsy sample, or who refuse to provide archival tissue are still eligible for the study.

Exclusion Criteria:

Participants must not be enrolled into the trial if one or more of the following criteria are met. Participants must NOT meet any of the following Exclusion criteria to be eligible for enrolment:

1. Known hypersensitivity to the investigational medicinal products (DOTA-STR-17126) or any of the excipients.
2. Participants with Class 3 or 4 New York Heart Association (NYHA) Congestive Heart Failure.
3. 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.
4. Clinically significant bleeding within two weeks prior to trial entry (i.e., gastrointestinal bleeding, intracranial bleeding).
5. Pregnant or lactating women. i. For female participants of childbearing potential or male participants with female partner of childbearing potential, who are not willing to practice highly effective contraception during the trial and for at least 6 months after [177Lu] Lu-DOTA-STR-17126 administration ii. Sexually active males must use a condom during intercourse while taking the drug and for 4 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Female partners of childbearing potential should use highly effective contraceptive methods during and up to 6 months after stopping treatment.
6. Have any medical condition that impairs complete bladder emptying. Participants with permanent urinary indwelling catheter (IDC) or nephrostomy may be allowed to enrol on a case-by-case basis in discussion with Principal Investigator, if it is determined not to put the patient at an increased risk of adverse drug effects and/or interfere with the integrity of study outcome.
7. Major surgery, defined as any surgical procedure that involves general anaesthesia and a significant incision (i.e., larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 30 days before study day 1 or anticipated surgery within the subsequent 43 days (6 weeks).
8. Has an additional active malignancy requiring therapy within the past 2 years.

9. History of another malignancy within 3 years before study enrolment. A subject with the following malignancies is allowed if considered cured or unlikely to recur within 3 years:

   i. Carcinoma of the skin without melanomatous features ii. Curatively treated cervical carcinoma in situ iii. Bladder tumours considered superficial such as non-invasive (T1a) and carcinoma in situ (T1s), thyroid papillary cancer with prior treatment

10. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy within 30 days prior to trial enrolment.
11. Psychiatric illness/social situations that would interfere with compliance with study requirements.
12. Cannot undergo PET/CT scanning because of weight limits (350 lbs or 160 kg).
13. Prior exposure to any other GRPR-targeting therapeutic agents.

14. Prior treatment with any systemic anti-cancer therapy including chemotherapy, immunotherapy, biological therapy, radiation therapy, biologic, hormonal or herbal therapy, or any investigational therapy or investigational device, unless:

    i. Standard of care or maintenance therapy such as, luteinizing hormone-releasing hormone (LHRH) or gonadotropin releasing hormone (GnRH) for patients with prostate cancer; selective estrogen receptor modulators or aromatase inhibitors or GnRH inhibitors for breast cancer, ii. Within more than 30 days of chemotherapy, herbal therapies and monoclonal antibodies, iii. Within more than 5 half-lives for biologic/non-cytotoxic targeted agents, iv. Within more than 8 weeks prior radiation therapies External Beam Radiotherapy (EBRT) and/or Radioligand Therapy (RLT). Focal palliative radiotherapy given within 8 weeks prior to the low dose of [177Lu] Lu-DOTA-STR-17126 may be approved on a case-by-case basis, if it is determined not to put the participant at an increased risk of adverse drug effects and/or interfere with the integrity of study outcome, v. For participants who received radiotherapy (EBRT and/or RLT) more than 8 weeks prior to the low dose of 177Lu-DOTA-STR-17126, efforts should be made to calculate the prior radiation absorbed dose to each critical organ such as the kidneys, liver, lungs, and bone marrow.

15. Patients with a history of inflammatory disease which according to the investigator may interfere with correct evaluation of radioactive uptake, especially those affecting the thoraco-abdominal cavities (i.e., autoimmune, granulomatous disease).
16. Any clinically significant toxicity (with the exception of alopecia) related to prior anti-tumour therapy not resolved to Grade 1 or baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: [68Ga]Ga-DOTA-STR-17126 and Low Dose [177Lu]Lu-DOTA-STR-17126; The intervention involves administration of two radiopharmaceuticals under investigation: Part 1: [68Ga] Ga-DOTA-STR-17126 is used as a PET imaging tracer to identify tumour lesions with high expression of GRPR. Participants will receive a single intravenous bolus dose of 150+/-50MBq (50 micrograms) of DOTA-STR-17126 precursor. Part 2: Participants who have GRPR positive lesions identified by [68Ga] Ga-DOTA-STR-17126 PET imaging will receive a low Dose [177Lu] Lu-DOTA-STR-17126. Eligible participant(s) will receive 1.0+/-0.5GBq (50 microgram peptide) dose of [177Lu] Lu-DOTA-STR-17126, administered as a slow intravenous infusion. SPECT/CT scans will be performed to assess the biodistribution, dosimetry, and extrapolation of potential therapeutic dose potential of the radiopharmaceutical.

Drug: [177Lu]Lu-DOTA-STR-17126; Participants 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.; Drug: [68Ga]Ga-DOTA-STR-17126; Participants will receive a single intravenous bolus dose of 150+/-50MBq (25 - 50 micrograms) of [68Ga]Ga-DOTA-STR-17126 precursor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 2 post-dose
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.	Day 2 post-dose
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.	Day 2 post-dose
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)	Day 1 post-dose, Day 2, Day 4, Day 8
Percentage of injected activity (%IA) in tumour and non-tumour organs	Calculate retention pattern within body and blood pool by the percentage of injected activity (%IA) in tumour and non-tumour organs	Day 1 post-dose, Day 2, Day 4, Day 8
Calculation of absorbed dose (AD, mGy/MBq)	Calculation of absorbed dose (AD, mGy/MBq) and effective whole-body dose (ED, mSv/MBq) of [68Ga]Ga-DOTA-STR-17126 and [177Lu]Lu-DOTA-STR-17126 The dosimetry analysis will enable estimated radiation absorbed doses from the radioligand therapeutic drug candidate [177Lu]Lu-DOTA-STR-17126 in organs and tumour lesions per unit administered activity (Gy/GBq).	Day 1 post-dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Pre-dose
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	Pre-dose

Collaborators and Investigators

• Sponsor: Integrated Haematology and Oncology Network
• Investigators: Principal Investigator: Nat Lenzo, MD, Integrated Hematology Oncology Network (Icon Group)

Study record dates

Study Major Dates

• Study Start (Estimated): May 3, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Neoplasms; Prostatic Neoplasms; Breast Neoplasms
• Other Study ID Numbers: 2025-11-1840

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Future use of research data Data collected during the study may be utilised in future research by the Principal Investigators, Sponsor and collaborating researchers to advance knowledge about cancer and its treatments. Proposals for access to trial data must be reviewed and approved by the PI.

Participants in this study will be asked to grant advanced permission for the possible future sharing of the data collected in this study. Additional participant consent for use of the data will only be sought if it is a requirement of the HREC.

• IPD Sharing Time Frame: 2029 for 12 months
• IPD Sharing Access Criteria: Email the study's central contact, provide a reason for your request, subject to review by the PI and Sponsor Oversight committee. You may be required to enter into a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No