SAR-BBN Radiotracers for Prostate Cancer

(COMBAT Trial)

Recruiting at 7 trial locations

Overseen By Clarity Pharmaceuticals

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Clarity Pharmaceuticals Ltd

Must be taking: Androgen deprivation

Must not be taking: Systemic radionuclides, Chemotherapy

Disqualifiers: Brain metastasis, Leukemia, DVT, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

38 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim for this study is to determine the safety and efficacy of 67Cu-SAR-BBN in participants with Gastrin Releasing Peptide Receptor (GRPR)-expressing metastatic castrate resistant prostate cancer in patients who are ineligible for therapy with 177Lu-PSMA-617.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like systemic anti-cancer therapy must be stopped at least 4 weeks before starting the trial, except for specific hormone therapies and low-dose corticosteroids.

What data supports the effectiveness of the treatment 64Cu-SAR-BBN for prostate cancer?

Research shows that copper-64 (64Cu) is effective in imaging and potentially treating prostate cancer due to its ability to target specific receptors on cancer cells. In a study, a similar treatment using copper-67 (67Cu) significantly inhibited tumor growth in mice, suggesting that copper-based treatments like 64Cu-SAR-BBN could be promising for prostate cancer. ^{1 2 3 4 5}

Is 64Cu-SAR-BBN safe for use in humans?

In a Phase I trial involving 64Cu-SAR-BBN PET-CT imaging for breast cancer, no adverse events were reported, suggesting it is generally safe for human use. ^{2 3 4 5 6}

What makes the SAR-BBN radiotracers unique for prostate cancer treatment?

The SAR-BBN radiotracers, using copper isotopes like 64Cu and 67Cu, are unique because they target the gastrin-releasing peptide receptor (GRPR) which is overexpressed in prostate cancer cells, allowing for both precise imaging and targeted therapy. This dual capability, known as theranostics, enables the same compound to be used for both diagnosing and treating cancer, which is not common in many existing treatments. ^{2 3 4 5 6}

Research Team

Clarity Pharmaceuticals

Principal Investigator

Clarity Pharmaceuticals

Eligibility Criteria

This trial is for adults with metastatic castrate resistant prostate cancer that expresses GRPR, who can't have 177Lu-PSMA-617 therapy. They must have good kidney function, progressive bone disease visible on scans, and a positive PET/CT scan with 64Cu-SAR-BBN. Participants need to be ineligible for certain other treatments and recovered from previous therapies' side effects.

Inclusion Criteria

Have progressive metastatic castration-resistant prostate cancer (mCRPC) despite prior androgen deprivation therapy (ADT) and at least either enzalutamide and/or abiraterone (or other such androgen receptor pathway inhibitors). Documented progressive mCRPC will be based on at least 1 of the following criteria: Serum/plasma prostate specific antigen (PSA) progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal value for study enrollment is 2.0 ng/mL; Soft-tissue progression defined as a ≥20% increase in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since the last treatment directed at the metastatic cancer has started (not including hormonal therapy) or the appearance of 1 or more new lesions; Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan. Participants must be ineligible for 177Lu-PSMA-617 therapy based on the following criterion: Uptake of 68Ga-PSMA-11 or 18F-DCFPyL in all lesions is negative (equal to or lower than that of liver parenchyma), or any one lesion larger than the size criteria is negative [size criteria: organs ≥1 cm, lymph nodes ≥2.5 cm, bones(soft tissue component) ≥1 cm]. Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (prior chemotherapy, radiation, immunotherapy, etc.); Participants must have adequate organ function: Bone marrow reserve: White blood cell (WBC) count ≥2.5 x 109/L (2.5 x 109/L is equivalent to 2.5 x 103/μL and 2.5 x K/μL and 2.5 x 103/cc and 2500/μL) OR Absolute neutrophil count (ANC) ≥1.5 x 109 /L (1.5 x 109 /L is equivalent to 1.5 x 103 /μL and 1.5 x K/μL and 1.5 x 103 /cc and 1500/μL); Platelets ≥100 x 109 /L (100 x 109 /L is equivalent to 100 x 103 /μL and 100 x K/μL and 100 x 103 /cc and 100,000/μL); Hemoglobin ≥9 g/dL (5.59 mmol/L); Total bilirubin ≤1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted; Alanine aminotransferase or aspartate aminotransferase ≤3.0 x ULN OR ≤5.0 x ULN for participants with liver metastases; Estimated glomerular filtration rate (eGFR) ≥50 mL/min For participants who are human immunodeficiency virus infected: Participant must be healthy and have a low risk of Acquired Immune Deficiency Syndrome related outcomes in the opinion of the Investigator; For participants who have partners of childbearing potential: Partner and/or participant must use a method of birth control with adequate barrier protection.

My prostate cancer diagnosis was confirmed through lab tests.

I have at least one cancer spread that shows on recent scans.

Exclusion Criteria

Previous treatment with any investigational agents within 4 weeks prior enrollment into the study

I was diagnosed with a blood clot in my leg or lung in the last 4 weeks.

My prostate cancer is of the small cell type.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive up to 2 administrations of 64Cu-SAR-BBN and single or multiple administrations of 67Cu-SAR-BBN based on cohort allocation

Up to 8 weeks

Cohort Expansion

Participants receive up to 3 administrations of 64Cu-SAR-BBN and 2 administrations of 67Cu-SAR-BBN at the recommended dose level

Up to 14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• 64Cu-SAR-BBN
• 67Cu-SAR-BBN

Trial Overview The study tests the safety and effectiveness of two radioactive drugs, 64Cu-SAR-BBN and 67Cu-SAR-BBN, in targeting GRPR-expressing prostate cancer cells in patients who cannot receive another specific treatment (177Lu-PSMA-617).

Participant Groups

Group I: 67Cu-SAR-BBN Experimental Treatment 2 Interventions

In the dose escalation phase: 64Cu-SAR-BBN: Patients will receive up to 2 administrations of 200MBq 67Cu-SAR-BBN: Cohorts 1 - 3: Single administration (dose will be determined based on cohort allocation). Cohort 4: 2 administrations at the recommended dose (determined by cohorts 1-3). In the cohort expansion phase: Patients will receive up to 3 administrations of 200MBq of 64Cu-SAR-BBN and 2 administrations at the recommended dose level of 67Cu-SAR-BBN, determined through the dose escalation. Additional administrations: (up to a maximum total of 4) may be offered to those participants, in either the dose escalation or cohort expansion, with radiological non-progression.

Who Is Running the Clinical Trial?

Clarity Pharmaceuticals Ltd

Lead Sponsor

Trials

11

Recruited

720+

Findings from Research

Copper-64 (64Cu) is a promising PET/CT tracer for diagnosing various cancers, including prostate cancer and glioblastoma, due to its ability to target copper-avid tumors and its favorable nuclear properties for both imaging and therapy.

Studies indicate that 64CuCl2 is safe in terms of radiation and toxicology, making it a viable option for theragnostic applications in oncology, particularly for imaging and potentially treating cancers like hepatocellular carcinoma and malignant melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent. Capriotti, G., Piccardo, A., Giovannelli, E., et al.[2023]

The study demonstrated that the targeted copper theranostic agent [67Cu]Cu-SAR-BBN effectively binds to GRPR-positive prostate cancer cells, achieving over 52% binding, which is significantly higher than the control.

In a pre-clinical mouse model, treatment with [67Cu]Cu-SAR-BBN resulted in a remarkable 93.3% inhibition of tumor growth and increased median survival from 34.5 days in the control group to over 54 days, indicating strong therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer. Huynh, TT., van Dam, EM., Sreekumar, S., et al.[2023]

The study shows that the CB-TE2A chelation system significantly improves the in vivo stability and clearance of 64Cu bombesin analogs in a prostate cancer mouse model, leading to better targeting of the BB2 receptor with reduced nontarget retention.

In comparison to the DOTA chelation system, the CB-TE2A system resulted in lower liver uptake and higher overall clearance of the radioconjugate, indicating its potential for enhanced safety and efficacy in diagnostic imaging and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems. Garrison, JC., Rold, TL., Sieckman, GL., et al.[2016]

The study involving seven patients with metastatic ER+/PR+/HER2- breast cancer demonstrated that [64Cu]Cu-SAR-BBN PET/CT is safe, with no adverse events reported, and it may provide valuable diagnostic information, especially for the lobular subtype of breast cancer.

[64Cu]Cu-SAR-BBN PET/CT showed higher uptake (mean SUVmax of 20) compared to [18F]FDG (mean SUVmax of 11) in lobular breast cancer, suggesting it may be more effective in detecting certain types of metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

64Cu-SAR-Bombesin PET-CT Imaging in the Staging of Estrogen/Progesterone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients: Safety, Dosimetry and Feasibility in a Phase I Trial. Wong, K., Sheehan-Dare, G., Nguyen, A., et al.[2023]

Copper-64 (64Cu) is being explored as a promising alternative to existing radiopharmaceuticals like gallium-68 and lutetium-177 for targeting neuroendocrine tumors and prostate cancer due to its unique nuclear properties that allow for both imaging and therapeutic effects.

64Cu can specifically target cancerous cells and may help detect early metastatic processes, leveraging its biological role in cellular functions, which enhances its potential as a theranostic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging value of 64Cu for molecular imaging and therapy. Bolzati, C., Duatti, A.[2021]

The study developed copper-64 radiolabeled BBN(7-14)NH(2) conjugates that effectively target gastrin-releasing peptide receptors (GRPr) in human prostate cancer, showing high receptor-binding affinity in PC-3 cancer cells.

In vivo tests in tumor-bearing mice demonstrated that these conjugates had high uptake in GRPr-positive tissues and produced clear microPET images of tumors, suggesting their potential for effective prostate cancer imaging in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [64Cu-NO2A-(X)-BBN(7-14)NH2], in a prostate tumor xenografted mouse model. Lane, SR., Nanda, P., Rold, TL., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Copper-67-Labeled Bombesin Peptide for Targeted Radionuclide Therapy of Prostate Cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems. [2016]

4. Switzerland pubmed.ncbi.nlm.nih.gov

64Cu-SAR-Bombesin PET-CT Imaging in the Staging of Estrogen/Progesterone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients: Safety, Dosimetry and Feasibility in a Phase I Trial. [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

The emerging value of 64Cu for molecular imaging and therapy. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [64Cu-NO2A-(X)-BBN(7-14)NH2], in a prostate tumor xenografted mouse model. [2019]