64Cu-LNTH-1363S for Sarcoma and Gastrointestinal Cancer

(PHANTOM Trial)

Recruiting at 2 trial locations

Overseen By Eryn Bagley

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lantheus Medical Imaging

Must not be taking: QT prolonging drugs

Disqualifiers: Pregnancy, Breastfeeding, Heart failure, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, open-label, prospective Phase 1/2a study to assess safety and tolerability, establish dosimetry and to identify an optimal imaging dose (radioactivity and mass dose) and imaging time window of 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent) and to compare its imaging biodistribution with FAP expression by immunohistochemistry (IHC) in patients with sarcomas or GIT cancers. The study will be conducted in 2 parts (Part 1 and Part 2).

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

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking medications known to cause QT prolongation, you may be excluded from the trial.

What data supports the effectiveness of the drug 64Cu-LNTH-1363S for sarcoma and gastrointestinal cancer?

Research shows that fibroblast activation protein inhibitors (FAPIs), like those used in 64Cu-LNTH-1363S, have been effective in improving imaging contrast in sarcoma and gastrointestinal cancer. Studies with similar FAPI-based imaging agents have demonstrated promising results in diagnosing and managing these cancers, suggesting potential effectiveness for 64Cu-LNTH-1363S. ^{1 2 3 4 5}

How is the drug 64Cu-LNTH-1363S unique for treating sarcoma and gastrointestinal cancer?

64Cu-LNTH-1363S is unique because it uses copper-64, a radioactive form of copper, to help visualize cancer cells through PET/CT imaging. This drug targets cancer cells by exploiting their increased uptake of copper, which is essential for their growth, making it a novel approach compared to traditional imaging methods. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults with certain types of sarcoma or gastrointestinal cancers, like esophageal, colorectal, stomach, and pancreatic cancer. Participants must have metastatic sarcoma confirmed by medical tests and adequate kidney function. Women who can bear children and men able to father a child must use effective contraception.

Inclusion Criteria

I am a man who can father children and agree to use contraception and not donate sperm during and for 28 days after the study.

I am eligible for Part 1 of the study.

My sarcoma is suspected to express FAP and has spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 2 weeks

Intervention

Participants receive 64Cu-LNTH-1363S imaging agent and undergo PET/CT scans to determine biodistribution and dosimetry

1 day

1 visit (in-person)

Safety Follow-up

Participants are monitored for safety and tolerability, including cardiac safety and adverse events

7 days

1 visit (in-person or virtual)

Scheduled Surgery and IHC Sample Collection

Participants undergo surgery for IHC sample collection to correlate imaging results with FAP expression

Up to 60 days post-intervention

Follow-up

Participants are monitored for safety and effectiveness after the intervention and surgery

4 weeks

Treatment Details

Interventions

• 64Cu-LNTH-1363S

Trial Overview The study is testing the safety and optimal imaging dose of a new PET/CT scan agent called 64Cu-LNTH-1363S in two parts. It aims to see how well this agent shows up on scans compared to the actual presence of FAP (a protein) in tumors.

Participant Groups

Group I: Experimental Part 2 Experimental Treatment 1 Intervention

Part 2 will evaluate 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent) correlation with FAP expression measured by IHC (SUVmax and SUVmean vs IHC score) in 20 evaluable patients with non-metastatic, operable, supposed FAP-expressing solid tumors (sarcomas, esophageal, gastric, pancreatic, colorectal) planned for surgery within 60 days (from study imaging).

Group II: Experimental Part 1 Experimental Treatment 1 Intervention

Six patients with metastatic sarcoma will receive 8 ± 1 millicurie (mCi) (\~50 μg mass dose) of 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent). Six patients with metastatic sarcoma will receive 8 ± 1 millicurie (mCi) (\~90 μg mass dose) of 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT Imaging Agent).

64Cu-LNTH-1363S is already approved in United States for the following indications:

Approved in United States as 64Cu-LNTH-1363S for:

• Sarcoma
• Esophageal Cancer
• Gastric Cancer
• Pancreatic Cancer
• Colorectal Cancer

Who Is Running the Clinical Trial?

Lantheus Medical Imaging

Lead Sponsor

Trials

57

Recruited

4,333,000+

Findings from Research

In a study involving 15 patients with sarcomas, the use of 68Ga-FAPI-PET/CT demonstrated excellent tumor-to-background ratios, indicating its potential effectiveness in accurately imaging sarcomas.

The highest uptake of the imaging probe was observed in liposarcomas and high-grade tumors, suggesting that 68Ga-FAPI-PET/CT could be particularly useful for identifying more aggressive forms of sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT. Koerber, SA., Finck, R., Dendl, K., et al.[2022]

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]

In a study of 45 patients with recurrent soft tissue sarcoma, [68 Ga]Ga-DOTA-FAPI-04 PET/CT detected significantly more lesions (275) compared to [18F]FDG PET/CT (186), demonstrating superior sensitivity, specificity, and overall accuracy for diagnosing recurrent lesions.

[68 Ga]Ga-DOTA-FAPI-04 PET/CT showed higher uptake values in specific sarcoma types like liposarcoma and malignant solitary fibrous tumor, making it a promising imaging tool for recurrent surveillance in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head-to-head evaluation of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma. Gu, B., Liu, X., Wang, S., et al.[2022]

The novel FAPI-04 dimer, labeled with radionuclides, significantly improves tumor retention time and uptake in cancer-associated fibroblasts, enhancing imaging and therapeutic effectiveness compared to previous FAPI designs.

In vivo studies demonstrated that the FAPI-04 dimer not only provided high-contrast imaging but also effectively slowed tumor growth, indicating its potential as a promising tool for both diagnosis and treatment in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Preclinical Evaluation of a Novel FAPI-04 Dimer for Cancer Theranostics. Zhong, X., Guo, J., Han, X., et al.[2023]

In a study of 35 patients with recurrent or metastatic gastrointestinal stromal tumors (GISTs), [18F]FAPI-42 PET/CT was found to be significantly more effective than [18F]FDG PET/CT, detecting 35.8% more lesions, particularly in liver metastases (87.5% vs. 33.3%).

The uptake of FAPI correlated with the level of fibroblast activation protein (FAP) expression in tumors, indicating that FAPI imaging is not influenced by tumor size, enhancement degree, or gene mutations, making it a potentially superior imaging biomarker for GISTs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]FAPI-42 PET/CT versus [18F]FDG PET/CT for imaging of recurrent or metastatic gastrointestinal stromal tumors. Wu, C., Zhang, X., Zeng, Y., et al.[2022]

Copper-64 chloride (64CuCl2) is a promising radiotracer for cancer imaging using PET, showing safety in humans and effective imaging for various cancers including prostate, bladder, and glioblastoma.

The dual emission of β+ and β- particles from 64CuCl2 suggests its potential not only for imaging but also for therapeutic applications in treating copper-avid tumors, especially with the development of the therapeutic copper-67 radionuclide for combined imaging and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in Cancer Imaging with 64CuCl2 PET/CT. Peng, F.[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]

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 Copper-64 labeled monoclonal antibodies (1A3 and its fragments) provide superior tumor imaging capabilities compared to traditional 111In and 125I labeled antibodies in a hamster model, indicating enhanced sensitivity for PET imaging of colorectal cancer.

While 64Cu-benzyl-TETA-1A3 shows promise for clinical use in PET imaging, the high kidney uptake of its fragment 64Cu-benzyl-TETA-1A3-F(ab')2 currently limits its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Copper-64-labeled antibodies for PET imaging. Anderson, CJ., Connett, JM., Schwarz, SW., et al.[2016]

Copper-64 (64Cu) is a versatile radionuclide with a half-life of 12.7 hours, making it suitable for both PET imaging and targeted radiotherapy of cancer, allowing for the imaging of various biological molecules and nanoparticles.

The FDA has approved an investigational new drug application for 64Cu-ATSM, a hypoxia imaging agent, which sets the stage for a multicenter trial aimed at validating its clinical utility and potentially leading to routine clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Copper-64 radiopharmaceuticals for PET imaging of cancer: advances in preclinical and clinical research. Anderson, CJ., Ferdani, R.[2023]

References

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

Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

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

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

Head-to-head evaluation of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma. [2022]

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

Synthesis and Preclinical Evaluation of a Novel FAPI-04 Dimer for Cancer Theranostics. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

[18F]FAPI-42 PET/CT versus [18F]FDG PET/CT for imaging of recurrent or metastatic gastrointestinal stromal tumors. [2022]

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

Recent Advances in Cancer Imaging with 64CuCl2 PET/CT. [2023]

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

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

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

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

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

Copper-64-labeled antibodies for PET imaging. [2016]

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

Copper-64 radiopharmaceuticals for PET imaging of cancer: advances in preclinical and clinical research. [2023]