[225Ac]-FPI-1434 for Cancer

Not currently recruiting at 13 trial locations

Overseen By [e-mail]

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fusion Pharmaceuticals Inc.

Must not be taking: Radiopharmaceuticals, Anticancer agents

Disqualifiers: Uncontrolled brain metastasis, others

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

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-1434 Injection to evaluate its safety and effectiveness for individuals with advanced solid tumors. It examines the drug's efficacy and potential side effects, particularly for tumors unresponsive to standard treatments. The trial includes different groups, with some receiving single or multiple doses, sometimes alongside another drug, FPI-1175. Individuals with advanced cancers such as endometrial, cervical, ovarian, and certain types of breast cancer, who have not benefited from existing treatments, might be suitable candidates. Participants must have a tumor exhibiting specific characteristics in imaging tests. As a Phase 1 trial, this research aims to understand how the treatment functions in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had anticancer therapy or radiation therapy within 14 days before starting the trial.

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

Research shows that [225Ac]-FPI-1434 is a new treatment being tested for safety in people with certain types of cancer. This treatment combines a radioactive substance with an antibody to specifically target cancer cells.

Since this is the first time [225Ac]-FPI-1434 is being tested in humans, no previous safety data exists. The trial is in Phase 1, focusing on checking safety and finding the best dose. During this phase, researchers closely monitor participants for any side effects to assess how well people handle the treatment.

So far, no serious side effects have been reported, but it's important to remember that this is still an early stage of research. Participants are monitored carefully to ensure their safety as scientists learn more about how this treatment works in the body. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about [225Ac]-FPI-1434 because it offers a novel approach to treating various cancers, such as head and neck squamous cell carcinoma, endometrial cancer, and others. Unlike conventional treatments like chemotherapy and radiation, which can affect both healthy and cancerous cells, [225Ac]-FPI-1434 uses a targeted radioactive isotope to directly attack cancer cells, potentially reducing side effects. The treatment incorporates an active ingredient, Actinium-225, which delivers a powerful punch to tumor cells while sparing healthy tissue. Additionally, the combination with or without FPI-1175 (a cold antibody) allows for flexibility in treatment, potentially enhancing its effectiveness against difficult-to-treat cancers.

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

Research has shown that [225Ac]-FPI-1434 could be a promising treatment for various types of cancer. This trial will evaluate [225Ac]-FPI-1434 in different treatment arms, including single-dose and multi-dose escalation, with or without pre-administration of FPI-1175 (cold antibody). This treatment employs targeted alpha therapy, which delivers radiation directly to cancer cells, destroying them while sparing healthy cells. Similar treatments have effectively shrunk tumors and slowed cancer growth. Although limited data exists on [225Ac]-FPI-1434 in humans, early studies suggest it might be effective for treating solid tumors. This approach leverages the body's ability to specifically target cancer cells, potentially leading to better patient outcomes. ^{1 2 4 5 6}

Who Is on the Research Team?

Julia Kazakin, MD

Principal Investigator

Fusion Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, including specific types of breast, cervical, ovarian cancer and more. Participants must have a life expectancy over 3 months, measurable disease after standard treatments fail or are unsuitable, good organ function and performance status. They can't join if they've had extensive radiation to bone marrow recently, uncontrolled brain metastases or other active cancers within the last 3 years.

Inclusion Criteria

My advanced cancer does not respond to standard treatments, or I cannot or choose not to receive them.

My bone marrow is functioning well.

My cancer can be measured or evaluated by standard criteria.

Exclusion Criteria

I have received radiation treatment of more than 20 Gy to large bone marrow areas.

I have been treated with nitrosoureas or actinomycin-D before.

You have high levels of protein in your urine that could affect your health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Single and multi-dose escalation of [225Ac]-FPI-1434 with or without FPI-1175, cycles repeating every 42 days

6-8 weeks per cycle

Phase 2 Treatment

Evaluation of [111In]-FPI-1547 and [225Ac]-FPI-1434 with or without FPI-1175 in tumour-specific cohorts

Approximately 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks post final [225Ac]-FPI-1434 Injection

What Are the Treatments Tested in This Trial?

Interventions

• [225Ac]-FPI-1434 Injection

Trial Overview The study tests [225Ac]-FPI-1434 Injection's safety and effectiveness in patients whose tumors absorb another agent ([111In]-FPI-1547) used for imaging. It aims to find the highest dose patients can tolerate without severe side effects (MTD) and suggest a Phase 2 dose (RP2D).

How Is the Trial Designed?

Group I: [225Ac]-FPI-1434 Single-Dose Escalation Experimental Treatment 2 Interventions

Group II: [225Ac]-FPI-1434 Multi-Dose Escalation Experimental Treatment 3 Interventions

\[225Ac\]-FPI-1434 treatment with or without pre-administration of FPI-1175 (cold antibody).

Group III: [225Ac]-FPI-1434 Multi-Dose Experimental Treatment 3 Interventions

Phase 2 Tumour Cohort - Head \& Neck Squamous Cell Carcinoma (HNSCC), Endometrial Cancer, Cervical Cancer, Ovarian Cancer, Triple Negative Breast Cancer (TNBC), HER2-negative, Adrenocortical Carcinoma (ACC), Uveal Melanoma, \[225Ac\]-FPI-1434 treatment with or without pre-administration of FPI-1175 (cold antibody).

Group IV: FPI-1175 Cold Antibody Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Fusion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

590+

Published Research Related to This Trial

In a study of 296 metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223, the treatment was generally well tolerated, showing similar safety profiles regardless of prior chemotherapy history.

However, patients who had received two lines of prior chemotherapy experienced higher rates of treatment-emergent adverse events (TEAEs) and hematotoxicities, indicating that more advanced disease may influence treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety and effectiveness of radium-223 in Japanese patients with castration-resistant prostate cancer (CRPC) and bone metastasis: exploratory analysis, based on the results of post-marketing surveillance, according to prior chemotherapy status and in patients without concomitant use of second-generation androgen-receptor axis-targeted agents. Uemura, H., Masumori, N., Takahashi, S., et al.[2021]

The development of 225Ac-radiopharmaceuticals for targeted alpha therapy shows promise but faces significant challenges, including limited isotope availability and complex chemistry for isolation.

Efforts at TRIUMF, Canada's particle accelerator centre, are focused on addressing these challenges to enhance the clinical use of 225Ac in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of 225Ac Radiopharmaceuticals: TRIUMF Perspectives and Experiences. Robertson, AKH., Ramogida, CF., Schaffer, P., et al.[2020]

The study presents an optimized protocol for preparing Ac-225 labeled with PSMA-617, achieving a high yield of 85%-87% and radiochemical purity of 97%-99%, which is crucial for effective targeted alpha therapy in prostate cancer.

This method allows for a single-step, routine in-house radiolabeling process, making it a practical approach for delivering targeted treatment to patients with metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma. Thakral, P., Simecek, J., Marx, S., et al.[2022]

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 56 patients with metastatic castration-resistant prostate cancer (mCRPC) who had exhausted standard treatments, [225Ac]Ac-PSMA-617 targeted alpha therapy showed promising efficacy, with 91% of patients experiencing a decline in prostate-specific antigen (PSA) levels, and a median overall survival of 15 months.

The treatment was well-tolerated, with most adverse events being mild to moderate, such as transient fatigue in 70% of patients and xerostomia in about one-third, indicating that [225Ac]Ac-PSMA-617 could be a viable option for patients with advanced mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study. Ballal, S., Yadav, MP., Satapathy, S., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03746431

A Phase 1 Study of [225Ac]-FPI-1434 Injection This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, tolerability, PK, ...

2. dana-farber.org dana-farber.org/clinical-trials/19-824

A Phase 1/2 Study of [225Ac]-FPI-1434 Injection in Patients ... This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, tolerability, PK, and preliminary ...

3. withpower.com withpower.com/trial/phase-1-2019-dabcd

[225Ac]-FPI-1434 for Cancer Research shows that targeted alpha therapy using 225Ac, like in [225Ac]-FPI-1434, is promising for treating cancers, as similar treatments have shown positive ...

4. clinicalresearch.com clinicalresearch.com/en/find-trials/Study/NCT03746431

A Phase 1/2 Study of [225Ac]-FPI-1434 Injection This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, tolerability, PK, ...

5. trials.braintumor.org trials.braintumor.org/trials/NCT03746431

A Phase 1 Study of [225Ac]-FPI-1434 Injection - National Brain ... An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is ...

6. trialx.com trialx.com/clinical-trials/listings/276919/a-phase-12-study-of-225ac-fpi-1434-injection/?&radius=50

A Phase 1/2 Study of [225Ac]-FPI-1434 Injection Overview. This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, ...