225Ac-PSMA-Trillium for Advanced Prostate Cancer

(PAnTHA Trial)

Recruiting at 43 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks a safer and more effective treatment for metastatic castration-resistant prostate cancer (mCRPC), a type of prostate cancer that has spread and no longer responds to hormone therapy. It tests a new drug, 225Ac-PSMA-Trillium (also known as BAY3563254), which targets cancer cells and emits radiation to stop their growth. Participants will help researchers determine the best dose and understand the drug's effects on cancer and overall health. This trial suits those with mCRPC who have undergone prior treatments, including some chemotherapy and hormone therapies, but whose cancer continues to progress. Participants will receive the treatment intravenously every six weeks, with close monitoring of their health and cancer status. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that 225Ac-PSMA-Trillium is likely to be safe for humans?

Research shows that 225Ac-PSMA-Trillium is just beginning human testing, so limited safety information is available. However, similar treatments, such as 225Ac-PSMA-I&T and 225Ac-PSMA-617, have demonstrated promising safety results in other studies. These treatments target a specific protein on prostate cancer cells and have generally been well-tolerated.

In these studies, side effects varied, with some patients experiencing manageable issues like dry mouth or fatigue. Serious side effects were less common. This suggests that 225Ac-PSMA-Trillium might have a similar safety profile, but more data is needed for confirmation. As this is an early-phase trial, researchers are focusing on determining the safest dose and monitoring for any side effects. Participants will be closely observed to ensure their safety throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about 225Ac-PSMA-Trillium because it represents a novel approach for treating advanced prostate cancer that has developed resistance to traditional therapies. Unlike standard treatments like hormone therapy or chemotherapy, 225Ac-PSMA-Trillium uses a targeted radiopharmaceutical approach, which means it delivers radiation directly to cancer cells by attaching to a molecule called PSMA found on prostate cancer cells. This targeted delivery could potentially minimize damage to healthy cells and reduce side effects. Additionally, the use of Actinium-225 as a radioactive agent is relatively new and promising, as it releases highly potent alpha particles that can effectively kill cancer cells with precision. This makes 225Ac-PSMA-Trillium a potentially game-changing option for patients with limited treatment choices.

What evidence suggests that 225Ac-PSMA-Trillium could be an effective treatment for advanced prostate cancer?

Research has shown that 225Ac-PSMA-Trillium, also known as BAY3563254, may help treat advanced prostate cancer. This trial will explore its effectiveness in various treatment arms, including dose escalation and dose expansion groups. Studies using prostate cancer models have demonstrated that it can significantly slow tumor growth, suggesting it might work for cancer unresponsive to hormone therapy. This treatment delivers targeted radiation directly to cancer cells, potentially stopping their growth. Early findings indicate that it remains in the bloodstream longer and targets cancer cells while reducing exposure to healthy organs. Although human studies have provided limited information, these early results are promising for its potential to treat metastatic castration-resistant prostate cancer. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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 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 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 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 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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06217822

NCT06217822 | First-in-human Study of 225Ac-PSMA ...

The study treatment 225Ac-PSMA-Trillium, also called BAY3563254, is under development to treat advanced metastatic castration-resistant prostate cancer. It ...

2.

bayer.com

bayer.com/media/en-us/bayer-starts-phase-i-study-with-novel-targeted-radionuclide-therapy-225ac-psma-trillium-in-advanced-metastatic-prostate-cancer/

Bayer starts Phase I study with novel targeted radionuclide ...

The dose-escalation study (NCT06217822) will evaluate the safety, tolerability and efficacy of 225Ac-PSMA-Trillium in patients with advanced ...

3.

urologytimes.com

urologytimes.com/view/study-launches-of-225ac-psma-trillium-in-mcrpc

Study launches of 225Ac-PSMA-Trillium in mCRPC

Data showed that in prostate cancer models, 225Ac-PSMA-Trillium induced strong tumor growth inhibition. “Targeted radionuclide therapy is a ...

4.

trialx.com

trialx.com/clinical-trials/listings/287456/first-in-human-study-of-225ac-psma-trillium-bay-3563254-in-participants-with-advanced-metastatic-castration-resistant-prostate-cancer-mcrpc/

First-in-human Study of 225Ac-PSMA-Trillium (BAY ...

The study treatment 225Ac-PSMA-Trillium, also called BAY3563254, is under development to treat advanced metastatic castration-resistant prostate ...

5.

aacrjournals.org

aacrjournals.org/cancerres/article/84/7_Supplement/ND09/742756/Abstract-ND09-Actinium-225-PSMA-Trillium-BAY

Abstract ND09: Actinium-225 -PSMA-Trillium (BAY 3563254 ...

Preclinical in vivo investigation of selected compounds showed increased plasma residence time, reduced uptake in normal organs, strong uptake ...

6.

theranostictrials.org

theranostictrials.org/studies/clsupindl001l11ujhnhud8tu/study/NCT06217822

NCT06217822

A Phase 1 Open-label, First-in-human, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of 225Ac-PSMA-Trillium ...

7.

aacrjournals.org

aacrjournals.org/cancerres/article/84/6_Supplement/6033/737603/Abstract-6033-Preclinical-evaluation-of-an

Preclinical evaluation of an actinium-225 labeled PSMA ...

Abstract. PSMA is a clinically validated target for the treatment of mCRPC. Since the linear energy transfer and degree of induced DNA ...

8.

withpower.com

withpower.com/trial/phase-1-prostate-specific-membrane-antigen-psma-expression-2-2024-008f9

225Ac-PSMA-Trillium for Advanced Prostate Cancer

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 ...