FAP-2286 Imaging for Cancer

Overseen By Maya Aslam

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Thomas Hope

Disqualifiers: Non-compliance, Pregnancy

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

Compensation: Varies

Number of Visits: 1

131 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial team for guidance.

What data supports the effectiveness of the treatment FAP-2286, 68Ga-FAP-2286, 64Cu-FAP-2286 for cancer?

Research shows that 68Ga-FAP-2286 is effective in detecting cancer lesions, with higher accuracy and better image contrast than traditional methods like 18F-FDG PET/CT. It has shown promising results in identifying primary and metastatic cancer lesions, making it a potentially better diagnostic tool for certain cancer types. ^{1 2 3 4 5}

Is FAP-2286 safe for use in humans?

68Ga-FAP-2286 is considered a promising and safe option for cancer diagnosis, staging, and restaging, with studies showing it has good tumor detection rates and is a better alternative for certain cancer types compared to other imaging agents. ^{1 2 3 6 7}

How does the drug FAP-2286 differ from other cancer imaging options?

FAP-2286 is unique because it targets the fibroblast activation protein (FAP) on cancer-associated fibroblasts, providing higher tumor retention and better image contrast compared to traditional imaging agents like 18F-FDG. This makes it particularly effective for detecting cancers with low-to-moderate uptake of 18F-FDG, such as gastric, pancreatic, and hepatic cancers. ^{2 4 5 8 9}

What is the purpose of this trial?

This trial tests a new imaging dye that helps doctors see cancer spread in patients with various solid tumors. The dye sticks to a specific protein in cancer cells and lights up on scans.

Research Team

Thomas A. Hope, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with solid tumors, including specific cancers like breast, pancreatic, prostate, bladder, or colon cancer. Participants may be at initial high-risk stages or post-treatment with a risk of recurrence. They must understand and sign consent.

Inclusion Criteria

Ability to understand a written informed consent document, and the willingness to sign it.

My cancer type does not matter and it doesn't need to be measurable for this study group.

My doctor considers my cancer high risk and believes imaging could change my treatment plan.

Exclusion Criteria

Known pregnancy.

Unlikely to comply with protocol procedures, restrictions and requirements and judged by the Investigator to be unsuitable for participation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET imaging using 68Ga- or 64Cu-FAP-2286 to evaluate uptake and retention in solid tumors

1 week

Multiple imaging sessions within 1 week

Follow-up

Participants are monitored for safety and effectiveness after imaging

Up to 3 days

Follow-up visits for adverse event monitoring

Treatment Details

Interventions

• FAP-2286

Trial Overview The trial tests new imaging agents (68Ga- and 64Cu-FAP-2286) that bind to proteins often found in solid tumors. It aims to see how well these tracers can detect metastatic cancer using PET scans in various patient groups.

Participant Groups

Group I: Participants without metastatic disease (Cohort 3) Experimental Treatment 3 Interventions

Participants without metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if if clinically indicated.

Group II: Participants with metastatic disease (Cohort 2) Experimental Treatment 3 Interventions

Participants with metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if clinically indicated.

Group III: CLOSED - 68Ga-Dosimetry population (Cohort 1a) Experimental Treatment 2 Interventions

PET imaging will begin 30 +/-10 minutes, 60 +/-15 minutes and 120 +/-20 minutes after injection of 68Ga-FAP-2286. Contrast may be administered if clinically indicated.

Group IV: CLOSED - 64Cu-Dosimetry population (Cohort 1b) Experimental Treatment 2 Interventions

PET imaging will begin 60±15 minutes, 240±30 minutes after injection,and 24±2 hours after injection of 64Cu-FAP-2286. Contrast may be administered if clinically indicated.

Who Is Running the Clinical Trial?

Thomas Hope

Lead Sponsor

Trials

11

Recruited

1,800+

Society of Abdominal Radiology

Collaborator

Trials

4

Recruited

200+

Society of Abdominal Radiology

Collaborator

Clovis Oncology, Inc.

Industry Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Findings from Research

The novel radiolabeled compound 68Ga-OncoFAP shows high affinity for fibroblast activation protein (FAP) and demonstrates excellent properties for PET imaging, including high tumor uptake and favorable biodistribution in both preclinical and clinical settings.

In a study involving 12 patients, 68Ga-OncoFAP exhibited significant uptake in various cancers, with maximum standardized uptake values (SUVmax) indicating its potential as a powerful alternative to existing FAP tracers for cancer imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA. Backhaus, P., Gierse, F., Burg, MC., et al.[2022]

In a study involving 64 patients with various cancers, 68Ga-FAP-2286 PET/CT demonstrated significantly higher uptake in primary tumors and metastases compared to the standard 18F-FDG PET/CT, indicating improved diagnostic accuracy.

68Ga-FAP-2286 successfully visualized all primary tumors and showed superior lesion detection rates for lymph node and distant metastases, making it a promising alternative for cancers that typically show low uptake of 18F-FDG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using 68Ga-FAP-2286: Comparison with 18F-FDG and 68Ga-FAPI-46 in a Single-Center, Prospective Study. Pang, Y., Zhao, L., Meng, T., et al.[2023]

FAP-2287, a radiopharmaceutical targeting FAP in tumors, showed significant tumor growth inhibition and improved survival in mice with FAP-expressing tumors when combined with PD-1 antibody treatment.

The treatment increased the infiltration of CD8+ T cells in the tumors and activated immune responses, suggesting that FAP-targeted radiotherapy can enhance the effectiveness of immune checkpoint inhibitors in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibroblast activation protein targeted radiotherapy induces an immunogenic tumor microenvironment and enhances the efficacy of PD-1 immune checkpoint inhibition. Zboralski, D., Osterkamp, F., Christensen, E., et al.[2023]

In a study of 62 patients with pancreatic cancer, 68Ga-FAPI PET imaging demonstrated a significant association with histopathologic fibroblast activation protein (FAP) expression, indicating its potential as a reliable diagnostic tool.

68Ga-FAPI PET showed superior tumor detection rates compared to traditional imaging methods like 18F-FDG PET and contrast-enhanced CT, achieving 100% sensitivity and high positive predictive values, which could lead to better management of pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-Labeled Fibroblast Activation Protein Inhibitor (68Ga-FAPI) PET for Pancreatic Adenocarcinoma: Data from the 68Ga-FAPI PET Observational Trial. Kessler, L., Hirmas, N., Pabst, KM., et al.[2023]

Fibroblast activation protein (FAP) is a promising target for tumor imaging and therapy, as it is found in over 90% of epithelial cancers, making it a specific marker for these tumors with minimal expression in normal tissues.

The use of [68Ga]Ga-FAPI PET/CT in lung cancer shows high uptake and tumor-to-background ratios, outperforming [18F]FDG PET/CT in detecting lung cancer and its metastases, suggesting its potential for better diagnostic and prognostic capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance and Prospects of [68Ga]Ga-FAPI PET/CT Scans in Lung Cancer. Borgonje, PE., Andrews, LM., Herder, GJM., et al.[2023]

In a study involving 120 patients with gastrointestinal cancers, 68Ga-FAPI PET demonstrated a diagnostic accuracy of 95.0%, significantly outperforming conventional imaging and 18F-FDG PET, which had accuracies of 65.1% and 69.0%, respectively.

68Ga-FAPI PET not only provided more accurate staging but also revised treatment plans for 22.9% of patients compared to conventional imaging, highlighting its potential to significantly impact clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gallium-68-labeled fibroblast activation protein inhibitor PET in gastrointestinal cancer: insights into diagnosis and management. Qin, C., Song, Y., Gai, Y., et al.[2022]

The study evaluated two new PET tracers, 68Ga-FAPI-2 and 68Ga-FAPI-4, in 50 cancer patients, showing that they provide similar or better tumor-to-background contrast compared to the standard 18F-FDG, with no need for dietary restrictions before the scan.

Both tracers demonstrated a low uptake in normal tissues and a rapid clearance via the kidneys, making them promising tools for cancer diagnostics with effective imaging capabilities shortly after injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers. Giesel, FL., Kratochwil, C., Lindner, T., et al.[2021]

FAPI PET imaging outperformed traditional FDG PET/CT/MRI in detecting tumors and metastases in patients with pancreatic, gastric, and cholangiocarcinoma, based on a systematic review of 10 studies.

FAPI PET provided higher maximum standardized uptake values (SUVmax) and tumor-to-background ratios (TBRmax), indicating its potential for more accurate cancer staging and diagnosis, which supports the need for further clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FAPI PET versus FDG PET, CT or MRI for Staging Pancreatic-, Gastric- and Cholangiocarcinoma: Systematic Review and Head-to-Head Comparisons of Diagnostic Performances. Veldhuijzen van Zanten, SEM., Pieterman, KJ., Wijnhoven, BPL., et al.[2022]

FAP-2286, a peptide targeting fibroblast activation protein (FAP), showed high affinity and selectivity for FAP in various tumors, including pancreatic and breast cancers, indicating its potential as a targeted imaging and therapeutic agent.

In preclinical studies, 177Lu-FAP-2286 demonstrated significant antitumor activity with minimal side effects, such as weight loss, and outperformed another FAP-targeting agent (FAPI-46) in terms of tumor retention and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. Zboralski, D., Hoehne, A., Bredenbeck, A., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA. [2022]

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

PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using 68Ga-FAP-2286: Comparison with 18F-FDG and 68Ga-FAPI-46 in a Single-Center, Prospective Study. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Fibroblast activation protein targeted radiotherapy induces an immunogenic tumor microenvironment and enhances the efficacy of PD-1 immune checkpoint inhibition. [2023]

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

68Ga-Labeled Fibroblast Activation Protein Inhibitor (68Ga-FAPI) PET for Pancreatic Adenocarcinoma: Data from the 68Ga-FAPI PET Observational Trial. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Performance and Prospects of [68Ga]Ga-FAPI PET/CT Scans in Lung Cancer. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Gallium-68-labeled fibroblast activation protein inhibitor PET in gastrointestinal cancer: insights into diagnosis and management. [2022]

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

68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

FAPI PET versus FDG PET, CT or MRI for Staging Pancreatic-, Gastric- and Cholangiocarcinoma: Systematic Review and Head-to-Head Comparisons of Diagnostic Performances. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. [2022]