[225Ac]-FPI-2059 for Solid Cancers

No longer recruiting at 9 trial locations

Overseen By Clinical Trials Fusion Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: 3B Pharmaceuticals GmbH

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called [225Ac]-FPI-2059 for individuals with solid tumors expressing the neurotensin receptor 1 (NTSR1) protein. The primary goal is to assess the safety, tolerability, and behavior of this treatment in the body. Participants should have a tumor that is inoperable, recurrent, or metastatic, and they should have tried other treatments that were ineffective or unsuitable. This study may suit those with advanced solid tumors, such as pancreatic or colorectal cancer, who have not found relief with standard treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

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

Research has shown that specific safety information for [225Ac]-FPI-2059 is not yet available. This trial marks the first human testing of the treatment, so its safety remains under investigation. As a Phase 1 study, the primary goal is to assess how well participants tolerate the treatment and identify potential side effects. At this stage, researchers are just beginning to understand the treatment's safety, closely monitoring participants for any adverse effects, which is standard for early-stage trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about [225Ac]-FPI-2059 because it uses a unique mechanism to target solid cancers. Unlike traditional chemotherapy that attacks both cancerous and healthy cells, [225Ac]-FPI-2059 delivers a radioactive isotope, Actinium-225, directly to cancer cells, potentially minimizing damage to healthy tissue. This targeted approach aims to improve effectiveness while reducing side effects, making it a promising option compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that [225Ac]-FPI-2059, which participants in this trial may receive, may effectively treat solid cancers. This drug targets and attaches to a specific protein called neurotensin receptor 1 (NTSR1) found on some cancer cells. By doing this, it delivers a strong dose of alpha radiation directly to the tumor, helping to destroy cancer cells. Studies have found that this targeted method keeps the drug in the tumor longer, potentially increasing its effectiveness. Although this research remains in the early stages, the drug's mechanism suggests it could be a promising treatment for cancers with NTSR1. ^{1 2 4 5 6}

Who Is on the Research Team?

Aaron Enke

Principal Investigator

3B Pharmaceuticals GmbH

Are You a Good Fit for This Trial?

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.

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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?

3B Pharmaceuticals GmbH

Lead Sponsor

Trials

1

Recruited

10+

Fusion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

590+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05605522

NCT05605522 | A Study of [225Ac]-FPI-2059 in Adult ... This is a first-in-human Phase 1 clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and biodistribution of [225Ac]-FPI-2059 and ...

2. withpower.com withpower.com/trial/phase-1-carcinoma-squamous-cell-10-2022-aa4c7

[225Ac]-FPI-2059 for Solid Cancers · Info for Participants [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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10380274/

Targeted Alpha-Particle Therapy: A Review of Current Trials Another phase I study (NCT05605522) enrolling 42 patients is evaluating 225Ac-FPI-2059 in metastatic solid tumors that express NTSR1. Six solid ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-01627

FPI-2059 in Adult Participants With Solid Tumours - NCI This is a first-in-human Phase 1 clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and biodistribution of [225Ac]-FPI-2059 ...

5. fusionpharma.com fusionpharma.com/wp-content/uploads/2023/04/AACR-2023-NTSR1-poster-V4.pdf

NTSR1-targeted Alpha Therapeutic [225Ac]-FPI-2059 ... Here, we describe the therapeutic efficacy of an [225Ac]- conjugated, NTSR1 targeting small molecule in a colorectal cancer tumor model. Background. Background.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05605522?cond=FPI-2059%20&limit=10&rank=1

A Study of [225Ac]-FPI-2059 in Adult Participants With ... A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.