[225Ac]-FPI-1434 for Cancer

Recruiting at 3 trial locations

Overseen By [e-mail]

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

253 Participants Needed

Trial Summary

What is the purpose of this trial?

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 anti-tumour activity of \[225Ac\]-FPI-1434 (radioimmuno-therapeutic agent) in patients with solid tumours that demonstrate uptake of \[111In\]-FPI-1547 (radioimmuno-imaging agent), and to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of repeat doses of \[225Ac\]-FPI-1434 Injection in patients with solid tumours that demonstrate uptake of \[111In\]-FPI-1547 (radioimmuno-imaging agent).

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.

What data supports the effectiveness of the drug [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 results in prostate cancer by delivering radiation directly to cancer cells. ^{1 2 3 4 5}

Research Team

Julia Kazakin, MD

Principal Investigator

Fusion Pharmaceuticals Inc.

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

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

2. India 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. [2022]

3. Japan 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. [2021]

4. Germany 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. [2023]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Development of 225Ac Radiopharmaceuticals: TRIUMF Perspectives and Experiences. [2020]