Cu-SAR-bisPSMA for Prostate Cancer

(SECuRE Trial)

Recruiting at7 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Clarity Pharmaceuticals Ltd

Must be taking: Androgen deprivation therapy

Must not be taking: Systemic radionuclides, Chemotherapy

Disqualifiers: Brain metastasis, Leukemia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new radioactive treatment called 67Cu-SAR-bisPSMA in patients with advanced prostate cancer that has spread and does not respond to hormone treatments. The treatment works by sticking to cancer cells and using radioactivity to destroy them.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain cancer treatments, you may need to stop them a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that 67Cu-CuSarbisPSMA, a similar treatment, effectively slows tumor growth in prostate cancer models. Additionally, 64Cu-labeled PSMA ligands have demonstrated high tumor uptake and clear imaging of cancer lesions, suggesting potential for both diagnosis and therapy. ^{1 2 3 4 5}

Is Cu-SAR-bisPSMA safe for use in humans?

The studies on Cu-SAR-bisPSMA and related compounds show promising results for targeting prostate cancer, with high stability and specific uptake in tumors. However, some studies noted slow clearance from the kidneys and high liver uptake, which are important safety considerations. Overall, the compounds have shown potential for safe use in imaging and therapy, but more human studies are needed to fully understand their safety profile. ^{1 2 3 6 7}

What makes the drug 67Cu-SAR-bisPSMA unique for treating prostate cancer?

67Cu-SAR-bisPSMA is unique because it targets prostate-specific membrane antigen (PSMA) with a copper isotope, allowing it to both image and treat prostate cancer. This dual capability, known as theranostics, helps in precise targeting and monitoring of the cancer, which is different from traditional treatments that may not offer both diagnostic and therapeutic benefits. ^{1 2 3 8 9}

Research Team

Clarity Pharmaceuticals

Principal Investigator

Clarity Pharmaceuticals

Eligibility Criteria

Men over 18 with metastatic castrate resistant prostate cancer that's gotten worse despite treatment, and who have a certain level of organ function. They must not have brain metastases, small cell or neuroendocrine prostate cancer, recent major surgery, or other serious health issues. Participants need to use birth control if applicable.

Inclusion Criteria

My testosterone levels are very low.

My PET/CT scan shows a lesion with higher activity than my liver.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I haven't had certain radioactive treatments in the last 3-6 months.

I have a severe blockage in my urinary tract that can't be easily treated.

I have not received a transfusion just to qualify for this study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dosimetry Phase

Participants receive a single 200 MBq administration of 64Cu-SAR-bisPSMA to assess dosimetry

1 week

1 visit (in-person)

Dose Escalation Phase

Participants receive up to 2 administrations of 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA to determine the recommended dose

8 weeks

Multiple visits (in-person)

Cohort Expansion Phase

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

14 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• 64Cu-SAR-bisPSMA (Diagnostic Agent)
• 67Cu-SAR-bisPSMA (Radioisotope Therapy)

Trial Overview The trial is testing the safety and effectiveness of two radioactive drugs called 67Cu-SAR-bisPSMA and 64Cu-SAR-bisPSMA in targeting and treating advanced prostate cancer that shows up on special PET/CT scans.

Participant Groups

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

In the dosimetry phase patients will receive a single 200 MBq administration of 64Cu-SAR-bisPSMA. In the dose escalation phase patients will receive up to 2 administrations of 200 MBq of 64Cu-SAR-bisPSMA. In the cohort expansion phase patients will receive up to 3 administrations of 200 MBq of 64Cu-SAR-bisPSMA. In the dose escalation phase patients will receive up to 2 administrations of 67Cu-SAR-bisPSMA (dose will be determined based on cohort allocation). In the cohort expansion phase patients will receive 2 administrations of 67Cu-SAR-bisPSMA at the recommended dose level determined through dose escalation.

Who Is Running the Clinical Trial?

Clarity Pharmaceuticals Ltd

Lead Sponsor

Trials

11

Recruited

720+

Findings from Research

The study demonstrates that 67Cu-CuSarbisPSMA effectively inhibits tumor growth in prostate cancer models, showing similar efficacy to 177Lu-LuPSMA in a dose-dependent manner.

Both single and fractionated doses of 67Cu-CuSarbisPSMA resulted in comparable survival rates, indicating its potential as a viable therapeutic option for patients with PSMA-positive prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Efficacy of a Bivalent Inhibitor of Prostate-Specific Membrane Antigen Labeled with 67Cu. McInnes, LE., Cullinane, C., Roselt, PD., et al.[2022]

The novel 64Cu-labeled PSMA ligands demonstrated high serum stability and effective targeting of prostate tumors, with significant tumor uptake observed in preclinical studies, indicating their potential for accurate imaging and treatment.

In a patient application, the compound CA003 provided clear visualization of cancer lesions, supporting its use for diagnostics and therapy planning in prostate cancer, particularly in conjunction with the therapeutic isotope 67Cu.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes. Carlos Dos Santos, J., Beijer, B., Bauder-Wüst, U., et al.[2020]

In a study involving LNCaP tumor-bearing mice, treatment with 64Cu-DOTHA2-PSMA significantly improved survival compared to the control group receiving natCu-DOTHA2-PSMA, indicating its potential as an effective therapeutic option for prostate cancer.

The treatment with 64Cu-DOTHA2-PSMA showed acceptable safety, with normal red blood cell counts and no significant signs of radiation injury, although there was some concern regarding hepatic and gastrointestinal irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theranostic 64Cu-DOTHA2-PSMA allows low toxicity radioligand therapy in mice prostate cancer model. Milot, MC., Bélissant-Benesty, O., Dumulon-Perreault, V., et al.[2023]

In a study of 125 men with metastatic castrate-resistant prostate cancer treated with 177LuPSMA, personalizing treatment intervals based on early response biomarkers (PSA and SPECT imaging) led to improved progression-free survival (PFS) and overall survival (OS), with a median OS of 16.8 months overall.

The study found that 35% of patients could take treatment breaks after showing a marked response, resulting in a median PFS of 12.1 months for this group, compared to shorter PFS for those with less favorable responses, highlighting the potential for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient outcomes following a response biomarker-guided approach to treatment using 177Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT). Emmett, L., John, N., Pathmanandavel, S., et al.[2023]

Treatment with lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA) significantly reduces prostate-specific antigen (PSA) levels in patients with advanced metastatic prostate cancer, especially after the first treatment cycle.

The therapy shows a beneficial effect on reducing lymph node metastasis, while also indicating potential negative impacts on visceral metastasis, highlighting its efficacy in managing certain aspects of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. Rathore, R., Rangrej, SB., Kieme, I., et al.[2023]

The radiolabeled ligand [64Cu]PSMA-617 demonstrated high radiochemical purity (>99%) and specific uptake in prostate cancer cells, indicating its potential for effective PET imaging of prostate cancer.

In vivo studies showed that [64Cu]PSMA-617 successfully visualized tumor areas in mice, although it exhibited slow clearance from the kidneys and high uptake in the liver, suggesting that modifications to its structure could enhance its use in imaging and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of [64Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer. Cui, C., Hanyu, M., Hatori, A., et al.[2020]

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 64Cu-PSMA-BCH radiopharmaceutical demonstrated high stability and specificity for prostate-specific membrane antigen (PSMA), showing significantly higher uptake in PSMA-positive cancer cells compared to PSMA-negative cells, which suggests its potential effectiveness for prostate cancer imaging.

In clinical applications, delayed imaging at 6 and 24 hours post-injection improved tumor detection rates, indicating that this radiopharmaceutical could enhance the accuracy of targeted biopsies in patients with suspected prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

64Cu-PSMA-BCH: a new radiotracer for delayed PET imaging of prostate cancer. Liu, T., Liu, C., Zhang, Z., et al.[2021]

The study demonstrated that 64Cu labeling of PSMA I&T is highly effective, achieving over 95% labeling yield and maintaining over 90% stability in serum for up to 60 hours, making it a promising candidate for prostate cancer imaging.

In vivo tests showed that 64Cu-PSMA I&T specifically binds to prostate cancer cells (22RV1) significantly better than non-target cells (PC-3), with tumor uptake increasing over time, indicating its potential for effective PET imaging in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Feasibility of 64Cu-PSMA I&T PET for Prostate Cancer. Lee, CH., Lim, I., Woo, SK., et al.[2022]

References

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

Therapeutic Efficacy of a Bivalent Inhibitor of Prostate-Specific Membrane Antigen Labeled with 67Cu. [2022]

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

Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Theranostic 64Cu-DOTHA2-PSMA allows low toxicity radioligand therapy in mice prostate cancer model. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Patient outcomes following a response biomarker-guided approach to treatment using 177Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT). [2023]

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

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. [2023]

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

Synthesis and evaluation of [64Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer. [2020]

7. Italy pubmed.ncbi.nlm.nih.gov

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

8. Germany pubmed.ncbi.nlm.nih.gov

64Cu-PSMA-BCH: a new radiotracer for delayed PET imaging of prostate cancer. [2021]

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

The Feasibility of 64Cu-PSMA I&T PET for Prostate Cancer. [2022]