64Cu-GRIP B PET Imaging for Genitourinary Cancer

Overseen by Rahul Aggarwal, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Rahul Aggarwal

Must be taking: Immune checkpoint inhibitors

Disqualifiers: Pregnancy, Breastfeeding, Informed consent, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial uses a special imaging technique to help see how well the immune system is fighting advanced GU cancers. It targets patients with specific types of advanced cancers and works by highlighting areas where immune cells are attacking cancer cells. This can help predict how well treatments are working.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug 64Cu-GRIP B for genitourinary cancer?

Research on similar treatments shows that PET imaging using granzyme B-targeted radiotracers can effectively predict tumor responses to immunotherapy in various cancers. This suggests that 64Cu-GRIP B, which targets granzyme B, might also help in assessing and potentially improving treatment responses in genitourinary cancer. ^{1 2 3 4 5}

Is 64Cu-GRIP B PET Imaging safe for humans?

Preclinical studies on similar 64Cu-labeled compounds for imaging prostate cancer have shown favorable biodistribution and stability, with no significant safety concerns reported in animal models. However, specific human safety data for 64Cu-GRIP B is not available, so further clinical evaluation is needed to confirm its safety in humans. ^{5 6 7 8 9}

How does the 64Cu-GRIP B PET Imaging treatment differ from other treatments for genitourinary cancer?

64Cu-GRIP B PET Imaging is unique because it uses a radiotracer to noninvasively visualize and track immune cell activity, specifically targeting granzyme B, which is released by immune cells during an immune response. This approach allows for early assessment of how well a patient's immune system is responding to cancer treatment, potentially improving the precision of immunotherapy strategies. ^{1 2 3 4 10}

Research Team

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with advanced genitourinary cancers, such as kidney and urethral cancer. Participants must be over 18, not pregnant or breastfeeding, willing to use contraception, and have a good performance status (able to carry out daily activities). They should have adequate organ function and specific types of metastatic cancer confirmed by tests.

Inclusion Criteria

I am 18 years old or older.

My kidney or urinary cancer has spread and this is confirmed by tests.

The subject is able and willing to comply with study procedures and provide signed and dated informed consent

Exclusion Criteria

Is currently pregnant or breastfeeding

Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures

I am unable to give informed consent due to my age, health, or mental condition.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline PET Imaging

All participants receive 64Cu-GRIP B PET imaging at baseline to assess initial uptake

1 day

1 visit (in-person)

Follow-up Imaging

Participants in Cohorts B and C undergo additional PET scans at 8 weeks and at disease progression

8 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored for safety and effectiveness, with follow-up for up to 2 years

Up to 2 years

Treatment Details

Interventions

• 64Cu-GRIP B (Imaging Agent)

Trial Overview The study is testing a new imaging technique using Copper-64 labeled Granzyme B (64Cu-GRIP B) with PET scans in patients with advanced genitourinary malignancies. It aims to identify tumors that may respond well to immunotherapy based on the presence of certain immune cells within the tumor.

Participant Groups

Group I: Cohort D: 64Cu-GRIP B, Advanced malignancies Experimental Treatment 2 Interventions

participants with solid tumor malignancies will have longitudinal imaging performed prior to treatment outside of this study, 8 weeks following initiation of treatment, and the opportunity to have an optional scan at the time of progression.

Group II: Cohort C: 64Cu-GRIP B, mCRPC participants Experimental Treatment 2 Interventions

Participants with metastatic castration resistant prostate cancer (mCRPC)) will have longitudinal imaging performed prior to treatment outside of this study, 8 weeks following initiation of treatment outside of this study, and at the time of disease progression by Prostate Cancer Working Group 3 (PCWG3) criteria.

Group III: Cohort B: 64Cu-GRIP B, RCC and UC participants Experimental Treatment 2 Interventions

Participants with renal cell and urothelial carcinoma will have longitudinal imaging performed prior to treatment outside of this study with anti-programmed death-1 (PD-1)/anti-PD-1 ligand 1 (PD-L1) blockade (with or without concomitant anti-CTLA4 treatment), after 8 weeks of checkpoint blockade, and again at the time of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Group IV: Cohort A: 64Cu-GRIP B, Solid Tumor Malignancy participants Experimental Treatment 2 Interventions

Participants with solid tumor malignancies (3 males, 3 females), dosimetry calculation will be performed by obtaining whole body (vertex to thighs) PET images up to five time points from 0.5 to 24 hours post 64Cu-GRIP B injections. An additional intravenous line will be placed in the contra-lateral arm to collect blood for this group.

Who Is Running the Clinical Trial?

Rahul Aggarwal

Lead Sponsor

Trials

13

Recruited

550+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

U.S. Army Medical Research Acquisition Activity

Collaborator

Trials

26

Recruited

10,500+

Findings from Research

The study demonstrated that the PET imaging agent [18F]AlF-mNOTA-GZP can effectively differentiate between cancer treatment responders and non-responders in a mouse model, indicating its potential as a biomarker for assessing the effectiveness of combined chemotherapy and immune checkpoint inhibitor therapies.

The uptake of [18F]AlF-mNOTA-GZP was positively correlated with the presence of Granzyme B-expressing immune cells, such as GZB+ CD8+ T cells and GZB+ NK+ cells, suggesting that Granzyme B plays a crucial role in the immune response to treatment and can serve as a reliable indicator of tumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granzyme B PET Imaging of Combined Chemotherapy and Immune Checkpoint Inhibitor Therapy in Colon Cancer. Goggi, JL., Hartimath, SV., Xuan, TY., et al.[2022]

The study developed novel SPECT imaging probes, [111 In]IDT and [111 In]IDAT, which effectively target granzyme B, a promising biomarker for enhancing immune checkpoint inhibitor treatments.

In experiments with tumor-bearing mice, these probes demonstrated moderate accumulation in tumors, correlating with granzyme B expression, suggesting their potential utility in monitoring treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of 111 In-labeled tetrapeptide-based compounds as single-photon emission computed tomography imaging probes targeting granzyme B. Kazuta, N., Watanabe, H., Ono, M.[2023]

The PET imaging technique using the granzyme B-targeted radiotracer 68Ga-grazytracer can effectively predict tumor responses to immunotherapy, showing better sensitivity in distinguishing responders from nonresponders compared to traditional methods.

In a preliminary clinical trial with 5 patients, 68Ga-grazytracer was safe with no adverse events reported, and its PET results correlated well with clinical responses to immunotherapy, suggesting its potential for improving patient stratification and early response assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive interrogation of CD8+ T cell effector function for monitoring early tumor responses to immunotherapy. Zhou, H., Wang, Y., Xu, H., et al.[2022]

Granzyme B PET imaging using the targeted peptide GZP is a highly sensitive and specific method for early assessment of response to cancer immunotherapy, showing 93% sensitivity and 94% negative predictive value in predicting treatment outcomes.

The study demonstrated that GZP PET imaging can effectively compare the efficacy of different checkpoint inhibitor regimens, revealing that sequential dosing of PD-1 and CTLA-4 therapies is as effective as concurrent administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging. Larimer, BM., Bloch, E., Nesti, S., et al.[2020]

Radioimmunotherapy (RIT) using [64Cu]Cu-NOTA-panitumumab F(ab')2 showed no significant normal tissue toxicity in non-tumor-bearing mice, indicating a safety profile for this treatment approach.

Combining RIT with gemcitabine and the PARP inhibitor rucaparib improved treatment effectiveness for pancreatic cancer xenografts, leading to longer median survival, but tumors continued to grow exponentially, suggesting that [64Cu] may not be the best choice for RIT in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy of human pancreatic cancer xenografts in NOD-scid mice with [64Cu]Cu-NOTA-panitumumab F(ab')2 alone or combined with radiosensitizing gemcitabine and the PARP inhibitor, rucaparib. Boyle, AJ., Cao, PJ., Cai, Z., et al.[2022]

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]

A novel gastrin-releasing peptide receptor (GRPR) ligand, AMTG, shows promise for detecting and treating prostate cancer, especially in patients with PSMA-negative lesions, demonstrating high GRPR affinity and favorable biodistribution in preclinical studies.

In a proof-of-concept study, the 68Ga-labeled AMTG showed intense uptake in metastatic lesions in a patient with castration-resistant prostate cancer, indicating its potential for effective theranostic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Comparison of the 64Cu- and 68Ga-Labeled GRPR-Targeted Compounds RM2 and AMTG, as Well as First-in-Humans [68Ga]Ga-AMTG PET/CT. Koller, L., Joksch, M., Schwarzenböck, S., et al.[2023]

The new [64Cu]Cu-gastrin-releasing peptide receptor (GRPR)-targeting tracers demonstrated high binding affinity to GRPR, with IC50 values under 3 nM, indicating their potential effectiveness in targeting prostate cancer cells.

In preclinical studies with tumor-bearing mice, the tracers showed good tumor uptake and rapid clearance, supporting their potential as diagnostic PET imaging agents for GRPR-expressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of Novel 64Cu-Labeled Gastrin-Releasing Peptide Receptor Bioconjugates for PET Imaging of Prostate Cancer. Makris, G., Shegani, A., Kankanamalage, PHA., et al.[2021]

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 successfully developed a method using 64Cu-labeled anti-CD8 cys-diabody for PET imaging, allowing for the noninvasive tracking of CD8+ T cells in both normal and tumor tissues in mice, demonstrating its potential to assess immunotherapy responses.

ImmunoPET imaging effectively detected changes in CD8+ T-cell distribution in response to immunotherapy, indicating its ability to visualize treatment effects and potential off-target effects, such as liver and splenic hypertrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols. Seo, JW., Tavaré, R., Mahakian, LM., et al.[2019]

References

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

Granzyme B PET Imaging of Combined Chemotherapy and Immune Checkpoint Inhibitor Therapy in Colon Cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of 111 In-labeled tetrapeptide-based compounds as single-photon emission computed tomography imaging probes targeting granzyme B. [2023]

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

Noninvasive interrogation of CD8+ T cell effector function for monitoring early tumor responses to immunotherapy. [2022]

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

The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging. [2020]

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

Radioimmunotherapy of human pancreatic cancer xenografts in NOD-scid mice with [64Cu]Cu-NOTA-panitumumab F(ab')2 alone or combined with radiosensitizing gemcitabine and the PARP inhibitor, rucaparib. [2022]

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

Preclinical Comparison of the 64Cu- and 68Ga-Labeled GRPR-Targeted Compounds RM2 and AMTG, as Well as First-in-Humans [68Ga]Ga-AMTG PET/CT. [2023]

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

Preclinical Evaluation of Novel 64Cu-Labeled Gastrin-Releasing Peptide Receptor Bioconjugates for PET Imaging of Prostate Cancer. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols. [2019]