SAR-BBN Radiotracers for Prostate Cancer

(COMBAT Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment for a specific type of advanced prostate cancer that does not respond to standard hormone treatments. The treatment uses radiotracers, such as 64Cu-SAR-BBN and 67Cu-SAR-BBN, to track and target cancer cells in the body. Individuals with prostate cancer that has spread, progressed despite current treatments, and who cannot receive the typical 177Lu-PSMA-617 therapy might be suitable for this study. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 64Cu-SAR-BBN and 67Cu-SAR-BBN are generally safe. In studies, patients usually tolerated 64Cu-SAR-BBN well, with most side effects being mild and manageable, such as temporary nausea or tiredness. Serious side effects were rare.

Studies also found 67Cu-SAR-BBN to be well-tolerated. Participants mostly experienced mild side effects similar to those of 64Cu-SAR-BBN. The research aimed to determine the highest dose patients could take without severe side effects.

Both treatments are under study for their ability to target specific cancer cells. This targeted approach can help reduce side effects compared to more general treatments. While these results are promising, further studies are needed to confirm the safety and effectiveness of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, which often include surgery, radiation, and hormone therapy, the investigational treatments 64Cu-SAR-BBN and 67Cu-SAR-BBN offer a unique approach. These radiotracers use a targeted mechanism to deliver copper radioisotopes directly to prostate cancer cells, potentially allowing for precise imaging and treatment. This could mean fewer side effects and more effective monitoring compared to conventional methods. Researchers are excited about these treatments because they represent a new way to specifically target cancer cells, possibly leading to improved outcomes for patients.

What evidence suggests that 67Cu-SAR-BBN might be an effective treatment for prostate cancer?

Research has shown that 67Cu-SAR-BBN, a radiotracer studied in this trial, targets the Gastrin Releasing Peptide Receptor (GRPR), often present in advanced prostate cancer. Animal studies demonstrated promising results, indicating that 67Cu-SAR-BBN effectively attaches to these receptors and may slow tumor growth. Early human trials reported no major issues, and the treatment was well-tolerated. This suggests that 67Cu-SAR-BBN could be a promising option for patients unable to receive treatments like 177Lu-PSMA-617. While more research is needed to confirm its effectiveness in humans, these early findings offer hope for a new treatment approach. ^{6 7 8 9 10}

Who Is on the Research Team?

Clarity Pharmaceuticals

Principal Investigator

Clarity Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. claritypharmaceuticals.com claritypharmaceuticals.com/news/combat_fpi/

First patient treated with Cu-67 SAR-Bombesin in ... The aim for the trial is to determine the safety and efficacy of 67 Cu SAR-Bombesin in participants with GRPr expressing mCRPC who are ineligible for therapy ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05633160?spons=COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22Clarity%20Pharmaceuticals%20Ltd%22)&viewType=Table&rank=5

Study Details | NCT05633160 | 64Cu-SAR-BBN and 67CU ... 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 ...

3. prnewswire.com prnewswire.com/news-releases/first-patient-treated-with-cu-67-sar-bombesin-in-theranostic-prostate-cancer-trial-301945053.html

First patient treated with Cu-67 SAR-Bombesin in ... No issues were observed during the administration of 6GBq of 67Cu SAR-Bombesin and the participant continues to be followed for further safety ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9229378/

Copper-67-Labeled Bombesin Peptide for Targeted ... This study explores the therapeutic efficacy of [67Cu]Cu-SAR-BBN in a pre-clinical mouse model. The peptide was radiolabeled with 67Cu, and ...

5. claritypharmaceuticals.com claritypharmaceuticals.com/wp-content/uploads/2024/07/SNMMI-2024-COMBAT-Final.pdf

COMBAT: A study of 64Cu-SAR-BBN and 67Cu- ... Metastatic castrate-resistant prostate cancer (mCRPC) is an advanced and lethal form of prostate cancer (PC). Prostate-specific membrane antigen.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.TPS346

Assessment of safety and efficacy of 64 Cu-SAR-BBN in ... SABRE: Assessment of safety and efficacy of 64Cu-SAR-BBN in patients with PSMA-negative biochemical recurrent prostate cancer. · Abstract.

7. claritypharmaceuticals.com claritypharmaceuticals.com/pipeline/sar-bbn/

SAR-Bombesin - Next Generation, Highly Targeted Pan ... The aim for the study is to determine the safety and efficacy of 67Cu-SAR-Bombesin in participants with GRPr-expressing metastatic castrate resistant prostate ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05407311

Study Details | NCT05407311 | 64Cu-SAR-BBN for ... The aim of this study is to determine the safety and efficacy of 64Cu-SAR-BBN and determine the ability of 64Cu-SAR-BBN Positron emission tomography (PET)/ ...

9. jnm.snmjournals.org jnm.snmjournals.org/content/65/9/1371

Utility of 64 Cu-Sarcophagine-Bombesin PET/CT in Men with ... 64 Cu-SAR-BBN PET/CT demonstrated sites of disease recurrence in 44% of BCR cases with negative or equivocal 68 Ga-PSMA-11 PET/CT results.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9316435/

64Cu-SAR-Bombesin PET-CT Imaging in the Staging of ... This study assessed the safety and potential of [64Cu]Cu-Sarcophagine (SAR)-Bombesin PET/CT (BBN) in re-staging metastatic ER+/PR+/human ...