First-in-human Diagnostic Imaging Profile of the Theranostic Pair [68Ga]Ga-DOTA-STR-17126 and Low Dose [177Lu] Lu-DOTA-STR-17126 in Patients With Advanced or Metastatic Cancer

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.

What this study is about