[225Ac]-FPI-2059 for Solid Cancers

Recruiting at 8 trial locations

Overseen By Clinical Trials Fusion Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fusion Pharmaceuticals Inc.

Must not be taking: Chemotherapy, Immunotherapy, Hormonal therapy, others

Disqualifiers: CNS metastatic disease, Severe illness, 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: Unknown

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human Phase 1 clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and biodistribution of \[225Ac\]-FPI-2059 and \[111In\]-FPI-2058 in participants with neurotensin receptor 1 (NTSR1)-expressing solid tumours.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had anti-cancer therapy or radiation therapy within a certain time before starting the trial.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that you cannot have had certain anti-cancer therapies or radiation therapy recently. It's best to discuss your specific medications with the trial team.

What data supports the idea that [225Ac]-FPI-2059 for Solid Cancers is an effective treatment?

The available research does not provide specific data on the effectiveness of [225Ac]-FPI-2059 for Solid Cancers. However, it does mention that similar treatments using 225Ac, like 225Ac-PSMA-617, have shown good anti-tumor effects in prostate cancer patients. Additionally, targeted alpha-therapy, which includes treatments like 225Ac, is being actively researched and has shown promising results in cancer management. This suggests that [225Ac]-FPI-2059 might also be effective, but more specific studies are needed to confirm its effectiveness for Solid Cancers. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment [225Ac]-FPI-2059 for solid cancers?

Research on similar treatments, like 225Ac-PSMA-617, shows promising anti-tumor effects in prostate cancer, and targeted alpha-therapy using 225Ac is actively being explored with promising results in cancer management. ^{1 2 3 4 5}

What safety data is available for [225Ac]-FPI-2059 in treating solid cancers?

The provided research does not contain specific safety data for [225Ac]-FPI-2059 or its related compounds ([111In]-FPI-2058, FPI-2058, FPI-2059). The articles focus on other cancer treatments and their associated adverse events, such as androgen receptor pathway inhibitors, aflibercept, VEGFR2-targeted agents, avapritinib, and sorafenib. Therefore, no relevant safety data for [225Ac]-FPI-2059 is available in the given research. ^{6 7 8 9 10}

Is the drug [225Ac]-FPI-2059 a promising treatment for solid cancers?

[225Ac]-FPI-2059 is a promising drug for treating solid cancers because it targets cancer cells effectively, showing high tumor uptake and retention. This means it can stay in the tumor longer, potentially improving treatment outcomes. It also has good binding to cancer-related proteins, making it a strong candidate for both diagnosing and treating cancers. ^{11 12 13 14 15}

What makes the drug [225Ac]-FPI-2059 unique for treating solid cancers?

The drug [225Ac]-FPI-2059 is unique because it targets fibroblast activation protein (FAP), which is often found in cancer cells, using a radiolabeled approach that allows for both imaging and treatment. This dual function can potentially improve the precision of cancer therapy by directly targeting cancerous tissues while sparing healthy ones. ^{11 12 13 14 15}

Research Team

Joanne Schindler, MD, DVM

Principal Investigator

Fusion Pharmaceuticals Inc.

Eligibility Criteria

This trial is for adults with certain advanced solid tumors, including pancreatic, colorectal, prostate, stomach cancers and more. Participants must have a tumor that can be measured by RECIST v.1.1 criteria and express NTSR1 as confirmed by imaging after [111In]-FPI-2058 injection. They should have an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory), adequate organ function, and no effective standard therapy options left.

Inclusion Criteria

Measurable disease per RECIST v.1.1

Signed ICF prior to initiation of any study-specific procedures

My scans show a lesion that can be measured for the study.

Exclusion Criteria

I am not allergic to the treatment being studied.

I do not have a severe illness that would stop me from following the study's requirements.

My cancer has spread to my brain.

Treatment Details

Interventions

• [111In]-FPI-2058
• [225Ac]-FPI-2059

Trial Overview [225Ac]-FPI-2059 and [111In]-FPI-2058 are being tested for safety, tolerability, how the body processes them (pharmacokinetics), and where they go in the body (biodistribution) in patients with solid tumors expressing neurotensin receptor 1. This first-in-human Phase 1 trial aims to find out if these treatments are safe to use and how they affect participants' bodies.

Participant Groups

Group I: Phase 1 Dose Expansion Experimental Treatment 2 Interventions

Group II: Phase 1 Dose Escalation Experimental Treatment 2 Interventions

[225Ac]-FPI-2059 is already approved in United States for the following indications:

Approved in United States as [225Ac]-FPI-2059 for:

• Investigational - Solid tumors expressing neurotensin receptor 1 (NTSR1)

Who Is Running the Clinical Trial?

Fusion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

590+

Findings from Research

In a study of 150 men with metastatic castration-resistant prostate cancer treated with radium-223, the median overall survival was 14.5 months, highlighting its efficacy in improving survival for patients with bone metastases.

Key pre-treatment factors such as low albumin, high alkaline phosphatase, poor performance status, and high prostate-specific antigen levels were identified as predictors of poor survival, allowing for the development of a prognostic model to better select patients who may benefit from radium-223 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic factors that influence prognosis and survival outcomes in men with metastatic castration-resistant prostate cancer treated with Radium-223. Al-Ezzi, EM., Alqaisi, HA., Iafolla, MAJ., et al.[2022]

Radium-223 is a first-in-class radiopharmaceutical that targets bone metastases in castration-resistant prostate cancer, showing a significant improvement in overall survival compared to placebo in the ALSYMPCA phase III study.

The treatment is generally well tolerated, with low rates of severe side effects, making it a valuable option for patients with symptomatic bone metastases and no visceral metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 dichloride: a review of its use in patients with castration-resistant prostate cancer with symptomatic bone metastases. Shirley, M., McCormack, PL.[2021]

In a study of 127 patients with castration-resistant prostate cancer treated with radium-223, those with only known bone lesions had a median progression-free survival (PFS) of 11.3 months, significantly longer than 8.1 months for those with de novo lesions and 5.1 months for those with new progressive lesions, indicating that the type of bone metastasis affects treatment outcomes.

Factors such as the presence of new progressive lesions, poor performance status, high PSA levels, and short PSA doubling time were identified as independent predictors of worse PFS, suggesting that these factors should be considered when assessing patient suitability for Ra-223 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic changes of bone metastasis predict bone-predominant status to benefit from radium-223 dichloride for patients with castration-resistant prostate cancer. Hashimoto, K., Miyoshi, Y., Shindo, T., et al.[2021]

In a preliminary study of 21 patients with de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) who refused standard treatments, 225Ac-PSMA-617 showed a significant anti-tumor effect, with 95% of patients experiencing a decline in prostate-specific antigen (PSA) levels, and 86% achieving a decline of 50% or more.

The treatment was well tolerated, with the most common side effect being mild dry mouth in 94% of patients, suggesting that 225Ac-PSMA-617 could be a promising alternative therapy for mHSPC patients who decline standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings. Sathekge, M., Bruchertseifer, F., Vorster, M., et al.[2023]

223Ra dichloride (223RaCl2) was approved in 2013 as a significant advancement in targeted α-therapy for cancer, demonstrating a safe and effective management strategy, particularly for metastatic prostate cancer.

There is growing research into combining 223RaCl2 with other treatments and exploring new α-therapy agents like 225Ac, which shows promising results in preclinical and early clinical studies, indicating a robust future for targeted α-therapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted α-Therapy in Cancer Management: Synopsis of Preclinical and Clinical Studies. Jadvar, H.[2021]

In a meta-analysis of 13 trials involving 5,546 patients, sorafenib was associated with a 1.99% incidence of fatal adverse events (FAEs), significantly higher than control treatments, with a relative risk of 1.77.

Patients with lung and renal cancers showed particularly elevated risks of FAEs, highlighting the need for careful monitoring in these populations, as the most common causes of FAEs were hemorrhage and thromboembolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of treatment-related mortality with sorafenib in patients with cancer. Zhang, XJ., Zhang, TY., Yu, FF., et al.[2022]

A study analyzing 278,031 reports of drug-related adverse events in prostate cancer patients found that abiraterone acetate and apalutamide are associated with a higher risk of major adverse cardiovascular events (MACE) compared to enzalutamide.

Despite the increased risk of MACE with abiraterone acetate and apalutamide, the incidence of severe MACE was significantly lower, suggesting that while these drugs may pose a cardiovascular risk, the severity of the events may be less concerning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Adverse Events Associated With New-Generation Androgen Receptor Pathway Inhibitors (ARPI) for Prostate Cancer: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS). Liu, Y., Zhang, HM., Jiang, Y., et al.[2023]

Aflibercept, used in cancer treatment, was found to increase the risk of fatal adverse events (FAEs) in patients, with an overall incidence of 5.1% among 3,060 patients analyzed from ten clinical trials.

The most common causes of FAEs linked to aflibercept were infections (38.8%), hemorrhage (5.9%), and gastrointestinal perforation (5.9%), indicating that while aflibercept is effective, careful monitoring for these serious side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related mortality with aflibercept in cancer patients: a meta-analysis. Qi, WX., Tang, LN., Shen, Z., et al.[2021]

In a systematic review of 17 randomized controlled trials involving 6,982 patients with solid tumors, VEGFR2-targeted agents were found to have an overall incidence of fatal adverse events (FAEs) of only 1.7%.

The study concluded that the use of VEGFR2-targeted agents did not significantly increase the risk of FAEs compared to control treatments, indicating a favorable safety profile for these cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and Risk of Fatal Adverse Events in Cancer Patients Treated With Vascular Endothelial Growth Factor Receptor 2-Targeted Agents: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials. Zhao, B., Zhao, H., Zhao, J.[2020]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

In a study of 75 cancer patients, [68Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated a significantly higher detection rate for primary tumors (98.2%) compared to [18F] FDG PET/CT (82.1%), indicating its superior diagnostic capability.

[68Ga]Ga-DOTA-FAPI-04 PET/CT also outperformed [18F] FDG PET/CT in detecting lymph node involvement and metastases, with sensitivity rates of 86.4% versus 45.5% for lymph nodes and 83.8% versus 59.5% for bone and visceral metastases, highlighting its effectiveness in identifying metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer. Chen, H., Pang, Y., Wu, J., et al.[2021]

Using half-dose [68Ga]Ga-FAPI-04 in total-body PET/CT imaging allows for a reduced acquisition time of 120 seconds while still achieving a 100% tumor detection rate in 27 patients, indicating its efficacy in diagnosing malignant tumors.

The image quality remains acceptable at this reduced dose and time, making it a safer option for radiation-sensitive populations, such as children and pregnant women, who may require shorter imaging sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of acquisitions using total-body PET/CT with a half-dose [68Ga]Ga-FAPI-04 activity in oncology patients. Chen, Z., Wang, Y., Yang, X., et al.[2023]

The radiopharmaceutical [18F]AlF-NOTA-FAPI-04 PET/CT demonstrated a significantly higher diagnostic sensitivity (97.7%) for detecting primary gastrointestinal tumors compared to 18F-FDG PET/CT (72.7%), indicating its superior efficacy in cancer diagnosis.

In addition to better detection rates, [18F]AlF-NOTA-FAPI-04 PET/CT also revised final diagnoses in 31.7% of patients and influenced clinical management decisions for 21.7% of patients, highlighting its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F] AlF‑NOTA‑FAPI‑04 PET/CT as a promising tool for imaging fibroblast activation protein in gastrointestinal system cancers: a prospective investigation of comparative analysis with 18F-FDG. Yang, L., Xu, S., Cheng, L., et al.[2023]

The FAPI tetramer demonstrated significantly higher tumor uptake and longer retention in cancerous tissues compared to FAPI dimers and monomers, indicating its potential for improved diagnostic and therapeutic applications in cancer treatment.

In radioligand therapy studies, the 177Lu-labeled FAPI tetramer showed remarkable tumor suppression in mice, suggesting its efficacy as a promising radiopharmaceutical for targeted cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of FAPI Tetramers to Improve Tumor Uptake and Efficacy of FAPI Radioligand Therapy. Pang, Y., Zhao, L., Fang, J., et al.[2023]

In a study of 21 patients with newly diagnosed oesophageal cancer, 68Ga-FAPI PET/CT demonstrated significantly higher radiotracer uptake in primary tumors compared to 18F-FDG PET/CT, suggesting it may be more effective for imaging this type of cancer.

The use of 68Ga-FAPI PET/CT for delineating gross target volumes (GTV) in radiotherapy planning showed promising results, with some patients benefiting from improved target volume accuracy, potentially reducing the risk of missing tumor areas during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-fibroblast activation protein inhibitor PET/CT on gross tumour volume delineation for radiotherapy planning of oesophageal cancer. Zhao, L., Chen, S., Chen, S., et al.[2021]

References

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

Clinicopathologic factors that influence prognosis and survival outcomes in men with metastatic castration-resistant prostate cancer treated with Radium-223. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Radium-223 dichloride: a review of its use in patients with castration-resistant prostate cancer with symptomatic bone metastases. [2021]

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

Dynamic changes of bone metastasis predict bone-predominant status to benefit from radium-223 dichloride for patients with castration-resistant prostate cancer. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings. [2023]

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

Targeted α-Therapy in Cancer Management: Synopsis of Preclinical and Clinical Studies. [2021]

6. Thailand pubmed.ncbi.nlm.nih.gov

Risk of treatment-related mortality with sorafenib in patients with cancer. [2022]

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

Cardiovascular Adverse Events Associated With New-Generation Androgen Receptor Pathway Inhibitors (ARPI) for Prostate Cancer: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS). [2023]

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

Treatment-related mortality with aflibercept in cancer patients: a meta-analysis. [2021]

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

Incidence and Risk of Fatal Adverse Events in Cancer Patients Treated With Vascular Endothelial Growth Factor Receptor 2-Targeted Agents: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials. [2020]

10. England pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Feasibility of acquisitions using total-body PET/CT with a half-dose [68Ga]Ga-FAPI-04 activity in oncology patients. [2023]

13. Germany pubmed.ncbi.nlm.nih.gov

[18F] AlF‑NOTA‑FAPI‑04 PET/CT as a promising tool for imaging fibroblast activation protein in gastrointestinal system cancers: a prospective investigation of comparative analysis with 18F-FDG. [2023]

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

Development of FAPI Tetramers to Improve Tumor Uptake and Efficacy of FAPI Radioligand Therapy. [2023]

15. Ireland pubmed.ncbi.nlm.nih.gov

68Ga-fibroblast activation protein inhibitor PET/CT on gross tumour volume delineation for radiotherapy planning of oesophageal cancer. [2021]