232 Participants Needed

BAY3546828 for Prostate Cancer

Recruiting at 31 trial locations
BC
Overseen ByBayer Clinical Trials Contact
Age: 18+
Sex: Male
Trial Phase: Phase 1
Sponsor: Bayer
Must be taking: Novel androgen axis drugs
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

Researchers are looking for a better way to treat people who have advanced metastatic castration-resistant prostate cancer (mCRPC). In participants with metastatic castration-resistant prostate cancer (mCRPC), the cancer of the prostate has spread to other parts of the body (metastatic) and does not respond to the lowering of testosterone levels in the body (castration resistant). The cancer is 'advanced' and is unlikely to be cured or controlled with currently available treatments. Despite new treatment options for participant(s) with prostate cancer in recent years, the cancer often returns and worsens. The study treatment actinium-225-macropa-pelgifatamab (also called 225Ac-pelgi or BAY3546828) is a new type of treatment under development for participants with mCRPC who have already received available treatments or have few treatment options available. It works by binding to a protein on the surface of the cancer cells called prostate specific membrane antigen (PSMA). As it gives off a type of radioactivity that travels a very short distance, it kills the nearby (cancer) cells that express PSMA. The main purpose of this first-in-human study in participants with mCRPC is to learn: * How safe different doses of 225Ac-pelgi are. * To what degree medical problems caused by 225Ac-pelgi can be tolerated by the participants? * Which dose of 225Ac-pelgi is optimal for treatment (safe and working well)? * How good is 225Ac-pelgi's anticancer activity? To answer this, the researchers will look at: * The number and severity of medical problems that the participants have after treatment with 225Ac-pelgi (per dose level). * The ratio of medical problems and anticancer activity per dose. * Anticancer activity of the optimal 225Ac-pelgi dose as proportion of participants who have at least halved prostate-specific antigen (PSA) levels after 12 weeks of treatment or later and/or shrunken or no longer detectable tumors. * The lowest PSA level reached after treatment start. Doctors keep track of all medical problems (also called adverse events) that participants have during the study, even if they do not think that they might be related to the study treatment. Anticancer activity is measured using cancer imaging techniques and change in blood level of a protein called PSA. PSA is made by normal and by cancerous cells in the body. The PSA level is taken as a marker for prostate cancer development and is usually elevated in participants with mCRPC. In addition, researchers want to find out how 225Ac-pelgi moves into, through and out of the body. The study will have two parts. The first part, called dose escalation, is done to find the most appropriate dose and schedule that can be given in the second part of the study. For this, each participant will receive one of the predefined increasing doses of 225Ac-pelgi as an infusion into the vein. All participants in part 2, called dose expansion, will receive the most appropriate dose and schedule identified from the first part of the study. More than one dose level or schedule from part 1 may be tested. Both the participants and the study team know what treatment the participants will take. Participants in this study will take the study treatment 225Ac-pelgi once in a period of 6 weeks called a cycle. Each participant will have 4 of these treatment cycles, if the participant benefits from the treatment. Each participant will be in the study for up to nearly six years, including a first test (screening) phase of a maximum of 30 days, up to 12 months of treatment depending on the participant's benefit, and a follow-up phase of 60 months after the end of treatment. The following visits to the study site are planned: 2 during the screening phase, 8 in the first treatment cycle, 7 in subsequent cycles, and a visit 6 to 12 weeks after the last dose. In the following 12 months, visits are planned every 6 weeks and during the next 48 months phone calls or clinic visits are planned approximately every 12 weeks. In addition, a sub study during the dose escalation part will gather information on the distribution of the study treatment in the body, the proportion that binds to the cancer cells, and the resulting radiation at the tumor site. During the study, the study team will: * Do physical examinations * Check vital signs such as blood pressure, heart rate, and body temperature * Take blood, and urine samples * Examine heart health using echocardiogram and electrocardiogram (ECG) * Take tumor samples * Track 225Ac-pelgi in the body using gamma imaging (generally available at all study sites) * Check the tumor status using PET (positron emission tomography), CT (computed tomography) or MRI (magnetic resonance imaging) and bone scan * Ask questions about the impact of the disease on the participants' wellbeing and activities of daily life (Eastern Cooperative Oncology Group Performance status (ECOG PS)).

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 Actinium-225-macropa-pelgifatamab (BAY3546828) safe for humans?

Actinium-225 labeled PSMA therapy has been tested in prostate cancer and is expected to have fewer side effects compared to other treatments, with encouraging safety results.12345

Eligibility Criteria

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.
See 6 more

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.
See 4 more

Timeline

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

Treatment Details

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.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Dose expansion group C of BAY3546828Experimental Treatment1 Intervention
Participants with advanced mCRPC after prior Lutetium-177 labeled PSMA ligand (177Lu-PSMA) treatment.
Group II: Dose expansion group B of BAY3546828Experimental Treatment1 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 BAY3546828Experimental Treatment1 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 BAY3546828Experimental Treatment1 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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials
2,291
Recruited
25,560,000+
Founded
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Headquarters
Leverkusen, Germany
Known For
Pharmaceutical Innovations
Top Products
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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 profile image

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

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.
The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer.Afshar-Oromieh, A., Babich, JW., Kratochwil, C., et al.[2021]
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.
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]
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.
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]

References

The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer. [2021]
68Ga-PSMA PET/CT Replacing Bone Scan in the Initial Staging of Skeletal Metastasis in Prostate Cancer: A Fait Accompli? [2021]
Preclinical Evaluation of a Fibroblast Activation Protein and a Prostate-Specific Membrane Antigen Dual-Targeted Probe for Noninvasive Prostate Cancer Imaging. [2023]
Efficacy and Safety of Actinium-225 Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Prostate Cancer: A Systematic Review and Metanalysis. [2023]
68Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis. [2022]
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