225Ac-PSMA-Trillium for Advanced Prostate Cancer

(PAnTHA Trial)

Recruiting at 30 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bayer

Must be taking: LHRH, GnRH

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: PSMA-negative lesions, Recent anticancer therapy, others

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

Compensation: Varies

Number of Visits: 14

Duration: 24 weeks

235 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers are looking for a better way to treat participants who have metastatic castration-resistant prostate cancer (mCRPC). mCRPC is a cancer of the prostate (male reproductive gland found below the bladder) that has spread to other parts of the body. This type of prostate cancer does not respond to hormone treatment used to lower the level of testosterone, a male sex hormone, to prevent cancer from growing. The study treatment 225Ac-PSMA-Trillium, also called BAY3563254, is under development to treat advanced metastatic castration-resistant prostate cancer. It works by binding to PSMA and giving off radiation that can damage cancer cells and stop them from growing. The main purpose of this first-in-human study is to learn: * How safe is BAY3563254 in participants. * What is the recommended dose of BAY3563254 that is safe and works well that will be further tested in Part 2 of the study. * How well does BAY3563254 work in participants. To answer this, the researchers will look at: * The number and severity of medical problems including serious medical problems that participants experience after taking BAY3563254 * The number of dose-limiting toxicities (DLT) at each dose level. A DLT is a medical problem caused by a drug that is too severe to continue the use of that specific dose. * The number of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)) * The number of participants who have a decrease in the levels of PSA\* by at least 50% in their blood (also known as PSA50). PSA is a protein made by the prostate gland. High levels of PSA may indicate the presence of prostate cancer. * Participants' best response to treatment based on their PSA levels (also known as the best overall PSA response). The study will have two parts. The first part, called dose escalation, is done to find the most appropriate dose of BAY3563254 for use in the second part of the study. For this, each participant will receive one of different increasing amounts of BAY3563254. They will take BAY3563254 as an injection into a vein. All participants in the second part of the study, called dose expansion, will receive the most appropriate dose of BAY3563254 that was identified from the first part of the study. Participants in this study will take the study treatment once every 6 weeks, which is known as a treatment cycle. Each participant will have up to 4 of these treatment cycles, if the participant benefits from the treatment. Each participant will be in the study for approximately 6 years, including a screening phase of up to 30 days, 6 months of treatment depending on the participant's benefit, and a follow up phase of 60 months after the end of treatment. In addition, substudies performed during both dose escalation and dose expansion parts of the study will evaluate: * the clearance of radioactivity from the body over time * the doses of radiation that are delivered to normal organs and tumors During the study, the doctors and their study team will: * take blood and urine samples * check vital signs such as blood pressure, heart rate, and body temperature * examine heart health using electrocardiogram (ECG) * take tumor samples if required * check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and bone scan * check the tumor status using PET (positron emission tomography) * check the amount of radiation absorbed by tumors and normal organs using SPECT/CT (single-photon emission tomography and computed tomography scan) * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study. The treatment period ends with a visit in 6-12 weeks after the last BAY3563254 dose. About 6-12 weeks after the last dose and every 6 weeks thereafter, the study doctors and their team will check the participants' health and any changes in their cancer. This active follow-up period ends after 18 months. The long-term follow-up period will start after the end of the active follow-up visit and will continue for up to 60 months after the the last BAY3563254 dose. Participants will be contacted, typically by phone call or clinic visit, approximately every 12 weeks after the end of active follow-up.

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

The trial protocol does not specify if you need to stop taking your current medications. However, prior systemic anticancer therapy, including chemotherapy and certain other treatments, must be stopped at least 4 weeks before starting the study treatment, except for specific hormone therapies. It's best to discuss your current medications with the study team to understand any specific requirements.

What data supports the effectiveness of the treatment 225Ac-PSMA-Trillium for advanced prostate cancer?

Research shows that 225Ac-PSMA therapies, like 225Ac-PSMA-617, have been effective in treating advanced prostate cancer, especially in cases resistant to standard treatments. These therapies have demonstrated the ability to reduce tumor growth and improve survival rates in patients with metastatic castration-resistant prostate cancer. ^{1 2 3 4 5}

What safety data exists for 225Ac-PSMA-Trillium in humans?

Clinical data for similar treatments like 225Ac-PSMA-I&T and 225Ac-PSMA-617 show promising results with some side effects. In a study with 225Ac-PSMA-I&T, no acute toxicity was observed, but some patients experienced anemia (low red blood cell count) and xerostomia (dry mouth). Another study on 225Ac-PSMA-617 indicated it is generally safe, with manageable side effects. ^{1 5 6 7 8}

What makes the drug 225Ac-PSMA-Trillium unique for advanced prostate cancer?

The drug 225Ac-PSMA-Trillium is unique because it uses an alpha-emitting particle, Actinium-225, to target prostate-specific membrane antigen (PSMA) on cancer cells, potentially offering higher efficacy and fewer side effects compared to beta-emitting treatments like Lutetium-177. This approach is promising for patients with advanced prostate cancer that is resistant to other treatments. ^{1 3 6 7 9}

Eligibility Criteria

This trial is for men with advanced metastatic castration-resistant prostate cancer (mCRPC), which has spread and doesn't respond to hormone therapy. Participants should be able to undergo various tests, including blood work, heart exams, imaging scans like CT or MRI, and possibly provide tumor samples.

Inclusion Criteria

My prostate cancer has worsened despite treatment.

I am on a consistent dose of blood thinner medication.

My prostate cancer is advanced and does not have certain aggressive features.

Exclusion Criteria

I have not had previous radiopharmaceutical treatments.

I am experiencing side effects from cancer treatment that are moderate or worse.

I haven't had cancer treatment in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive BAY3563254 once every 6 weeks for up to 4 cycles, with dose escalation and expansion phases

24 weeks

1 visit every 6 weeks

Active Follow-up

Participants' health and cancer status are monitored every 6 weeks after treatment ends

18 months

1 visit every 6 weeks

Long-term Follow-up

Participants are contacted approximately every 12 weeks to monitor long-term outcomes

60 months

Contact every 12 weeks

Treatment Details

Interventions

• 225Ac-PSMA-Trillium (BAY3563254)
• Tris-POC (BAY2688901)

Trial Overview The study is testing a new treatment called BAY3563254 that targets prostate cancer cells with radiation. It's given as an injection every 6 weeks for up to 4 cycles. The first part of the study determines the safest dose; the second part uses this dose in more people.

Participant Groups

Group I: HPGe or NaI Whole Body Radioactivity Measurement of 225Ac-PSMA-Trillium Experimental Treatment 1 Intervention

HPGe or NaI measurements of whole-body radioactivity of 225Ac and its daughters as a function of time will be conducted on an optional basis during dose escalation and dose expansion at selected sites to evaluate the clearance of total radioactivity from the body over time. Participants in the 111In-PSMA-Trillium and Tris-POC Imaging Substudy will not be eligible for this HPGe or NaI Whole Body Radioactivity Measurement of 225Ac-PSMA-Trillium Substudy.

Group II: Dose expansion group C of BAY3563254 Experimental Treatment 1 Intervention

Participants with advanced mCRPC treated with 225Ac-PSMA-Trillium, who must have had prior treatment with 177Lu-PSMA more than 6 weeks before the start of study treatment and at least 1 but no more than 2 taxane regimens (or been deemed ineligible for or refused taxane therapy on consultation with their physician).

Group III: Dose expansion group B of BAY3563254 Experimental Treatment 1 Intervention

Participants with advanced mCRPC treated with 225Ac-PSMA-Trillium, who must not have received taxane-based chemotherapy since becoming castration resistant. Prior radiopharmaceutical treatment is not permitted.

Group IV: Dose expansion group A of BAY3563254 Experimental Treatment 1 Intervention

Participants with advanced mCRPC treated with 225Ac-PSMA-Trillium, who must have received at least 1 but no more than 2 prior taxane-based chemotherapy regimens. Prior radiopharmaceutical treatment is not permitted.

Group V: Dose escalation of BAY3563254 Experimental Treatment 1 Intervention

Participants with advanced mCRPC will receive increased 225Ac-PSMA-Trillium doses in a planned stepwise fashion.

Group VI: 225Ac-PSMA-Trillium Imaging and Dosimetry Experimental Treatment 1 Intervention

The 225Ac-PSMA-Trillium Imaging and Dosimetry Substudy will enroll throughout both dose escalation and dose expansion, starting with the first dose level in dose escalation. The substudy will generally be available at all study sites to participants in the main study.

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

The new α-particle-emitting compound 225Ac-L1 shows specific targeting and effective cell kill in prostate cancer cells that express PSMA, demonstrating significant tumor growth inhibition and improved survival in xenograft models.

While 225Ac-L1 has promising efficacy, it also presents some off-target radiotoxicity, particularly in the kidneys and liver, with a maximum tolerated dose estimated at about 1 MBq/kg, indicating a need for careful dosing in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of 213Bi- and 225Ac-Labeled Low-Molecular-Weight Compounds for Radiopharmaceutical Therapy of Prostate Cancer. Banerjee, SR., Lisok, A., Minn, I., et al.[2022]

In a pilot study of 30 patients with metastatic castration-resistant prostate cancer, 177Lu-PSMA-617 therapy led to a 73% PSA response after the first treatment cycle, indicating its efficacy in reducing cancer markers.

Quality of life significantly improved after two months of therapy, with notable enhancements in global health status, role functioning, and emotional well-being, alongside a reduction in pain, suggesting that PSA response is associated with these quality of life improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving quality of life in patients with metastatic prostate cancer following one cycle of 177Lu-PSMA-617 radioligand therapy: a pilot study. Marinova, M., Alamdar, R., Ahmadzadehfar, H., et al.[2021]

In a study of 12 patients with metastatic castration-resistant prostate cancer, 225Ac-PSMA therapy showed promising results, with 9 out of 12 patients exhibiting a PSA response after the first treatment cycle, and 6 achieving a significant reduction of over 50%.

The median overall survival for patients who responded to the therapy was 10 months, compared to 4 months for non-responders, suggesting that early PSA response may correlate with better survival outcomes, although the difference was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer: A Single-Center Experience. Sanli, Y., Kuyumcu, S., Simsek, DH., et al.[2023]

177Lu-PSMA is an effective treatment for advanced prostate cancer, lowering PSA levels and improving quality of life, but about one-third of patients may not respond well to this therapy, highlighting the need for better personalization of treatment.

225Ac-PSMA shows promise for tumors resistant to standard treatments, offering a better response than 177Lu-PSMA, but it poses risks of significant damage to healthy tissues, necessitating careful dosimetry and potential use of nano-carriers for safer delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of 177Lutetium-PSMA and 225Actinium-PSMA as Emerging Theranostic Agents in Prostate Cancer. Alam, MR., Singh, SB., Thapaliya, S., et al.[2022]

In a meta-analysis of 6 studies involving 201 patients with metastatic castration-resistant prostate cancer, 225Ac-PSMA-617 demonstrated a high efficacy, with 87% of patients showing any decrease in prostate-specific antigen (PSA) levels and 66% achieving a PSA decrease of more than 50%.

The treatment was found to be relatively safe, with the most common side effect being xerostomia (dry mouth) occurring in 77.1% of patients, but only 3% experiencing severe cases, indicating that 225Ac-PSMA-617 is a promising option with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis. Ma, J., Li, L., Liao, T., et al.[2022]

In a study of 14 patients with advanced metastatic castration-resistant prostate cancer, treatment with 225Ac-PSMA imaging and therapy (I&T) showed promising results, with 50% or greater declines in prostate-specific antigen (PSA) levels observed in 7 patients.

The treatment was well-tolerated, with no acute toxicity during hospitalization, although some patients experienced grade 3 anemia and leukopenia; importantly, preexisting xerostomia did not worsen in most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients. Zacherl, MJ., Gildehaus, FJ., Mittlmeier, L., et al.[2021]

Actinium-225 (Ac-225) PSMA radioligand therapy (RLT) shows promising efficacy in treating metastatic castration-resistant prostate cancer (mCRPC), with 81% of patients experiencing a decline in PSA levels and 60% achieving more than a 50% reduction.

The treatment is generally safe, with the most common side effect being mild to moderate xerostomia (dry mouth) reported in 73.9% of patients, indicating that Ac-225 may have fewer severe side effects compared to traditional beta-emitting therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Actinium-225 Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Prostate Cancer: A Systematic Review and Metanalysis. Parida, GK., Panda, RA., Bishnoi, K., et al.[2023]

In a study of 49 patients with advanced prostate cancer, treatment with 177Lu-PSMA after prior 223Ra therapy was found to be well tolerated, with manageable side effects such as anemia in 18% of patients.

The median overall survival for patients starting 177Lu-PSMA was 12.6 months, suggesting that using 223Ra before 177Lu-PSMA is a feasible treatment sequence that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Survival Outcomes of 177Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer with Prior 223Ra treatment: The RALU Study. Rahbar, K., Essler, M., Pabst, KM., et al.[2023]

177Lu-PSMA-617 is a promising new treatment for patients with advanced prostate cancer, specifically targeting the prostate-specific membrane antigen (PSMA) found on cancer cells.

The therapy was also experimentally applied to a female patient with metastasized leiomyosarcoma, suggesting potential for PSMA-targeted treatment in other types of tumors beyond prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. Jüptner, M., Marx, M., Zuhayra, M., et al.[2021]

References

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

Preclinical Evaluation of 213Bi- and 225Ac-Labeled Low-Molecular-Weight Compounds for Radiopharmaceutical Therapy of Prostate Cancer. [2022]

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

Improving quality of life in patients with metastatic prostate cancer following one cycle of 177Lu-PSMA-617 radioligand therapy: a pilot study. [2021]

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

225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer: A Single-Center Experience. [2023]

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

A Review of 177Lutetium-PSMA and 225Actinium-PSMA as Emerging Theranostic Agents in Prostate Cancer. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis. [2022]

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

First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Actinium-225 Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Prostate Cancer: A Systematic Review and Metanalysis. [2023]

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

Safety and Survival Outcomes of 177Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer with Prior 223Ra treatment: The RALU Study. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. [2021]