BAY3546828 for Prostate Cancer

Recruiting at 35 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Bayer

Must be taking: Novel androgen axis drugs

Must not be taking: Actinium-225, Radiopharmaceuticals

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: 16

Duration: 12 months

232 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Actinium-225-macropa-pelgifatamab (BAY3546828) for advanced prostate cancer that has spread and resists testosterone-lowering therapies. The researchers aim to determine if Actinium-225-macropa-pelgifatamab is safe, identify the optimal dose, and assess its effectiveness against cancer. Suitable participants have prostate cancer that worsens despite other treatments and exhibit high prostate-specific antigen (PSA) levels, a marker of prostate cancer. 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 therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain anticancer therapies within 4 weeks before starting the study treatment, except for specific hormone therapies. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that actinium-225-macropa-pelgifatamab (BAY3546828) could help treat advanced prostate cancer. This treatment targets a protein on cancer cells and uses radioactivity to destroy them. Early studies on similar treatments have shown they can be effective and safe for people with prostate cancer, but researchers are still learning about BAY3546828 specifically.

As this trial begins, the main goal is to ensure safety and determine the right dose. Researchers will carefully monitor for any side effects. Other studies with similar treatments have been well-tolerated, but every new treatment requires thorough evaluation. Participants in this study will undergo regular health checks to ensure their well-being. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike the standard treatments for advanced metastatic castration-resistant prostate cancer (mCRPC) that primarily focus on hormone therapy or chemotherapy, BAY3546828 uses a novel approach. This treatment involves Actinium-225, a radioactive isotope, which is linked to a targeting molecule called pelgifatamab. This combination aims to directly deliver radiation to cancer cells, potentially reducing damage to healthy tissue. Researchers are excited about BAY3546828 because it offers a targeted therapy option that could be effective for patients who have limited treatment choices, especially those who have already undergone other therapies without success.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research has shown that actinium-225-macropa-pelgifatamab (225Ac-pelgi) could be a promising treatment for advanced prostate cancer that no longer responds to hormone therapy. This trial will explore different dosing strategies of 225Ac-pelgi, including dose escalation and expansion groups, to assess its effectiveness and safety. The treatment targets a protein on cancer cells called PSMA and releases radiation to kill these cells. Early lab studies demonstrated that it can effectively shrink tumors in models of this type of prostate cancer. The treatment aims to lower PSA levels, which monitor prostate cancer growth. Although human studies provide limited information, the treatment's mechanism suggests it could benefit patients with advanced stages of the disease. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for men with advanced metastatic castration-resistant prostate cancer (mCRPC) who have tried other treatments or have limited options. They must have a specific type of prostate cancer, confirmed by tests, and treated previously with certain drugs like enzalutamide or abiraterone. Participants need to maintain low testosterone levels through treatment or surgery and should be physically able to perform daily activities with minimal assistance.

Inclusion Criteria

My scans show at least one PSMA-positive spot away from my prostate.

I have previously received 177Lu-PSMA therapy.

I have specific requirements for prior taxane treatment based on my treatment group.

Exclusion Criteria

I have received radiopharmaceutical treatments based on my treatment group.

I finished my last cancer treatment less than 6 weeks ago.

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

2 visits (in-person)

Treatment

Participants receive 225Ac-pelgi in cycles, with dose escalation and expansion phases to determine optimal dosing

12 months

8 visits in the first cycle, 7 visits in subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Visits every 6 weeks for 12 months, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Actinium-225-macropa-pelgifatamab (BAY3546828)

Trial Overview The study is testing the safety and effectiveness of a new treatment called Actinium-225-macropa-pelgifatamab (BAY3546828). It targets a protein on cancer cells to deliver radiation directly to them. The trial has two parts: finding the best dose and then giving that dose over four cycles every six weeks if beneficial. Researchers will monitor participants' health, take samples, use imaging techniques, and ask about their wellbeing.

How Is the Trial Designed?

Group I: Dose expansion group C of BAY3546828 Experimental Treatment 1 Intervention

Participants with advanced mCRPC after prior Lutetium-177 labeled PSMA ligand (177Lu-PSMA) treatment.

Group II: Dose expansion group B of BAY3546828 Experimental Treatment 1 Intervention

Participants with advanced mCRPC who have not received taxane chemotherapy since becoming castration-resistant. No prior radionuclide therapy.

Group III: Dose expansion group A of BAY3546828 Experimental Treatment 1 Intervention

Participants with advanced mCRPC with at least 1 but no more than 2 prior taxane regimens. No prior radionuclide therapy

Group IV: Dose escalation of BAY3546828 Experimental Treatment 1 Intervention

Participants with advanced metastatic castration-resistant prostate cancer (mCRPC) will receive 225Ac-pelgi dose in a stepwise fashion, according to a predefined dose escalation scheme

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

Prostate-specific membrane antigen (PSMA) has emerged as a key target for both imaging and therapy in prostate cancer, with significant advancements including the use of 68Ga-PSMA-11 for PET imaging and 177Lu-labeled ligands like PSMA-617 for therapy, which are currently being studied in multicenter trials.

The transition from 131I-related PSMA therapy to 177Lu-labeled ligands represents a major improvement in treatment options, enhancing the efficacy and safety of endoradiotherapy for metastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer. Afshar-Oromieh, A., Babich, JW., Kratochwil, C., 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 113 patients with prostate cancer, 68Ga-PSMA PET/CT demonstrated significantly higher sensitivity (96.2%) and accuracy (99.1%) for detecting skeletal metastases compared to traditional bone scintigraphy (73.1% sensitivity and 84.1% accuracy).

68Ga-PSMA PET/CT not only identified more bone lesions (91 vs. 61) but also revealed an additional 96 unexpected extraskeletal lesions, highlighting its superior capability in detecting both lytic and bone marrow metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-PSMA PET/CT Replacing Bone Scan in the Initial Staging of Skeletal Metastasis in Prostate Cancer: A Fait Accompli? Lengana, T., Lawal, IO., Boshomane, TG., et al.[2021]

68Ga-PSMA PET/CT is highly effective for detecting recurrent prostate cancer, identifying cancer sites in 81% of patients with rising PSA levels after treatment, and showing a 50% detection rate for PSA levels between 0.2-0.49 ng/ml.

The imaging method demonstrated no reported adverse effects, making it a safe option for patients, and it outperformed traditional imaging methods like bone scans in detecting early recurrence of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis. von Eyben, FE., Picchio, M., von Eyben, R., et al.[2022]

The novel imaging probe [68Ga]Ga-FAPI-PSMA shows high affinity for prostate cancer cells, making it effective for diagnostic imaging, with IC50 values of 4.73 nM for PSMA and 2.10 nM for FAP expressing cells.

In vivo studies demonstrated that [68Ga]Ga-FAPI-PSMA rapidly accumulates in prostate tumors and provides optimal imaging results at 1 hour post-injection, while also having a relatively low radiation dose compared to other imaging probes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of a Fibroblast Activation Protein and a Prostate-Specific Membrane Antigen Dual-Targeted Probe for Noninvasive Prostate Cancer Imaging. Wang, P., Wang, S., Liu, F., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06052306

NCT06052306 | A Study to Learn How Safe the ... The study treatment actinium-225-macropa-pelgifatamab (also called 225Ac-pelgi or BAY3546828) is a new type of treatment under development for participants with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38593212/

Preclinical Efficacy of a PSMA-Targeted Actinium-225 ... Here we introduce a targeted alpha therapy (TAT) consisting of the PSMA antibody pelgifatamab covalently linked to a macropa chelator and labeled with actinium ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/30/11/2531/745373/Preclinical-Efficacy-of-a-PSMA-Targeted-Actinium

Preclinical Efficacy of a PSMA-Targeted Actinium-225 ... Recently, beta emitter-based PSMA-targeted radionuclide therapy has been approved for the treatment of metastatic castration-resistant prostate cancer. We ...

4. theranostictrials.org theranostictrials.org/studies/clsupindl001l11ujhnhud8tu/study/NCT06052306

NCT06052306 The study treatment actinium-225-macropa-pelgifatamab (also called 225Ac-pelgi or BAY3546828) is a new type of treatment under development for men with mCRPC ...

5. urotoday.com urotoday.com/clinical-trials/prostate-cancer/148246-a-phase-1-open-label-first-in-human-multicenter-study-to-evaluate-the-safety-tolerability-pharmacokinetics-and-antitumor-activity-of-actinium-225-macropa-pelgifatamab-bay-3546828-in-participants-with-advanced-metastatic-castration-resistant-prostat.html?tags=14636

A Phase 1 Open-label, First-in-human, Multicenter Study to ... A Phase 1 Open-label, First-in-human, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39865485/

The Safety and Efficacy of Targeted Alpha Therapy, Ac-225 ... 225 Ac-PSMA RLT is an efficacious and safe treatment for mCRPC. Future well-designed randomized controlled studies comparing 225 Ac-PSMA RLT with other ...