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AzTrials

Metastatic Castration-resistant Prostate CancerPhase 1NCT06052306

A Study to Learn How Safe the Study Treatment Actinium-225-macropa-pelgifatamab (BAY3546828) is, How it Affects the Body, How it Moves Into, Through and Out of the Body, and About Its Anticancer Activity in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)

A Phase 1 study testing BAY3546828 in people with Metastatic Castration-resistant Prostate Cancer, run by Bayer at 11 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
BAY3546828
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
11 sitesin 4 countries
Study dates
20 Sep 2023to 10 Aug 2031
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • mCRPC with pathological confirmation of adenocarcinoma without small-cell or neuroendocrine features.
  • Previous treatment with at least 1 Novel androgen axis drug (NAAD) (e.g., enzalutamide, apalutamide, darolutamide and/or abiraterone).
  • Prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
  • Prior taxane treatment:
  • Dose Escalation: Participants must either have had prior treatment with at least 1 but no more than 2 taxane regimens, or been deemed ineligible for or refused taxane therapy on consultation with their physician
  • Dose Expansion Group A: Participants must have had prior treatment with at least 1 but no more than 2 taxane regimens, in the castration-resistant setting
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  • Dose Expansion Group B: Participants must not have received taxane therapy since becoming castration-resistant
  • Dose Expansion Group C: Participants must either have had prior treatment with at least 1 but no more than 2 taxane regimens*, or been deemed ineligible for or refused taxane therapy on consultation with their physician *A taxane regimen consists of a minimum of 2 treatment cycles (maximum number of cycles as per local guidelines). A treatment break within a taxane regimen may be given provided that another anticancer therapy is not administered during that time
  • Prior treatment with an established 177Lu-PSMA therapy (i.e., dose activity and cycles comparable to approved treatments) is required for participants in Dose Expansion Group C only. More specifically, to qualify for this expansion group, participants must not have discontinued 177Lu-PSMA tratment due to intolerance.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
  • Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements within 30 days before start of study intervention:
  • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count (ANC) ≥1500/mm^3
  • Platelet count ≥100,000/mm^3
  • Total bilirubin ≤1.5 x the Upper limit of normal (ULN), or <= 3 ULN if the participant has a confirmed history of Gilbert's syndrome (note that participants with Gilbert's syndrome should be carefully evaluated for other liver-related disorders that may impact their suitability for this study).
  • Alanine transaminase (ALT) and Aspartate transaminase (AST) ˂2.5 x ULN (≤5 x ULN for participants with liver involvement)
  • Participants on a stable dose of anticoagulation therapy are allowed to participate if they have no sign of bleeding or clotting, and Prothrombin time international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) test results are acceptable at the Investigator's discretion
  • Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m^2, according to the Modified Diet in Renal Disease (MDRD) abbreviated formula and creatinine clearance (CrCl) >60 mL/min based on Cockcroft-Gault formula
  • Participants must have at least one Prostate-specific membrane antigen (PSMA)-positive distant metastatic lesion on the screening PSMA PET/CT scan using the study-designated PSMA PET tracers, as determined by the site Investigator. For eligibility purposes, a PSMA-positive lesion must have activity greater than the liver by visual assessment of the screening PSMA PET/CT. A PSMA-positive metastatic lesion should not correspond to a normal tissue structure or benign lesion.
  • Documented progressive mCRPC per PCWG3, defined as meeting at least one of the following criteria:
  • PSA-progression (defined as 2 consecutive increases over a previous reference value obtained at a minimum of 1-week intervals, with a minimum starting value of 2.0 ng/mL)
  • Radiological progression in soft-tissue lesions according to PCWG3 modification of RECIST v1.1 criteria
  • Progression of bone disease (defined as ≥2 new bone lesions according to PCWG3 bone scan criteria).
  • Documented progressive mCRPC per PCWG3 and a minimun starting PSA value of 2.0 ng/mL is mandatory. Progressive mCRPC is defined as meeting at least one of the following criteria: a. PSA progression (defined as 2 consecutive increases over a previous reference value obtained at a minimun of 1-week intervals). b. Radiological progression in soft-tissue lesions according to PCWG3 modification of RECIST v1.1 criteria. c. Progression of bone disease (defined as ≥ 2 new bone lesions according to PCWG3 bone scan criteria).

Who cannot join

  • Participants who have any of the following tumor lesions which are PSMA negative AND meet the size criteria below are excluded as determined by the site investigator. A PSMA-negative lesion for eligibility purposes must have activity equal to or less than the liver by visual assessment of the screening PSMA PET/CT scan using the study-designated PSMA PET/CT tracers. A PSMA-negative metastatic lesion should not correspond to a normal tissue structure or benign lesion.
  • a. Any single or multiple lymph node(s) ≥2.5cm in the short axis.
  • b. Any solid organ metastasis (e.g., lung, liver, adrenal glands, etc.) that is ≥1 cm in the short axis.
  • c. Any bone metastasis with a soft tissue component ≥ 1cm in short axis with the soft tissue component being PSMA-negative. PSMA-negative osseous metastases without a soft tissue component do not exclude a participant.
  • d. Predominantly necrotic lesions with greater than 1cm of enhancing tissue on contrast-enhanced Computer tomography / magnetic resonance imaging (CT/MRI).
  • Prior systemic anticancer therapy including chemotherapy, NAAD, biologic therapy, immunotherapy, or investigational therapies within 4 weeks of the start of study intervention, except luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH). Start of study intervention is allowed in shorter timeframes if 5 half-lives of the prior drug(s) have elapsed.
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  • Prior radiopharmaceutical treatment using actinium-225.
  • Other prior radiopharmaceutical treatments:
  • Dose escalation and Dose expansion Groups A and B: Prior treatment with a radiopharmaceutical is prohibited.
  • Dose expansion Group C: Prior treatment with a radiopharmaceutical is prohibited with the following exceptions: Prior treatment with radium-223 dichloride more than 3 months before the start of study intervention is permitted; and prior treatment with 177Lu PSMA more than 6 weeks before the start of study intervention is required.
  • Note: Participants who have discontinued 177Lu-PSMA treatment due to intolerance are excluded from Group C.
  • Prior definitive therapy (radiotherapy or surgery) completed less than 6 weeks before the start of study intervention. Note that palliative radiotherapy completed less than 6 weeks before the start of study intervention will be allowed if: (i) no more than 10% of the participants' bone marrow is irradiated, (ii) it does not encompass all potential target/measurable lesions for participants in dose expansion.
  • Toxic effects of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from prior anticancer therapy not yet stabilized or where significant post-treatment toxicities have been observed. Chronic toxic effects of CTCAE Grade ≤2 from prior anticancer therapy where no further resolution is expected do not require exclusion with agreement between the Investigator and Sponsor (e.g., chemotherapy-induced neuropathy, fatigue, alopecia, anorexia, etc.).
  • Dose Expansion (Groups A, B and C): Presence of >3 liver metastases, any diffuse liver metastasis, or PSMA-non-avid liver metastasis (uptake is lower or equal compared to healthy liver tissue).

Trial locations and contacts

11 sites in 4 countries.

11 sites in 4 countries

Finland4 sites

  • HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Syöpäkeskus

    Helsinki, Uusimaa, 00029

  • Docrates Mehiläinen Syöpäsairaala

    Helsinki, Uusimaa, 00180

  • Kuopio University Hospital, Kuopion yliopistollinen sairaala (KYS) - Syövänhoitokeskus

    Kuopio, Northern Savonia, 70210

  • CRST Oy - Clinical Research Services Turku

    Turku, Southwest Finland, 20520

Other trials in Finland

United Kingdom3 sites

  • Addenbrooke's Hospital | Clinical Research Centre

    Cambridge, Cambridgeshire, CB2 0QQ

  • University College Hospital | NIHR UCLH Clinical Research Facility

    London, Greater London, W1T 7HA

  • The Royal Marsden (Surrey) | Oak Foundation Drug Development Unit

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Canada2 sites

  • Centre Hospitalier de l'Universite de Montreal (CHUM) | Oncology

    Montreal, Quebec, H2X 0C1

  • Research Institute of the McGill University Health Centre | McConnell Centre for Innovative Medicine

    Montreal, Quebec, H4A 3J1

Other trials in Canada

Netherlands2 sites

  • Universitair Medisch Centrum Groningen

    Groningen, 9713 GZ

  • Erasmus Medisch Centrum

    Rotterdam, South Holland, 3015 CE

Other trials in Netherlands

About this study

Official title: 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 Prostate Cancer (mCRPC)

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.

Read more

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)).
Being tested
BAY3546828

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BAY3546828Drug

    Intravenous (IV) infusion on Day 1 of each cycle.

Study groups in NCT06052306
Study groupRoleWhat they receive
Dose escalation of BAY3546828ExperimentalParticipants with advanced metastatic castration-resistant prostate cancer (mCRPC) will receive 225Ac-pelgi dose in a stepwise fashion, according to a predefined dose escalation scheme
Receives: Drug: BAY3546828
Dose expansion group A of BAY3546828ExperimentalParticipants with advanced mCRPC with at least 1 but no more than 2 prior taxane regimens. No prior radionuclide therapy
Receives: Drug: BAY3546828
Dose expansion group B of BAY3546828ExperimentalParticipants with advanced mCRPC who have not received taxane chemotherapy since becoming castration-resistant. No prior radionuclide therapy.
Receives: Drug: BAY3546828
Dose expansion group C of BAY3546828ExperimentalParticipants with advanced mCRPC after prior Lutetium-177 labeled PSMA ligand (177Lu-PSMA) treatment.
Receives: Drug: BAY3546828

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose escalation & Dose expansion: The Incidence of treatment-emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs)

    Measured: After first administration of study treatment up to 42 days after the last dose of study treatment

  2. Dose escalation & Dose expansion: The Severity of TEAEs including TESAEs

    Measured: After first administration of study treatment up to 42 days after the last dose of study treatment

  3. Dose escalation: Incidence of dose limiting toxicities (DLTs) at each 225Ac dose level during the DLT observation period

    DLTs will be summarized by MedDRA system organ class, preferred term and worst CTCAE grade.

    Measured: Up to Cycle 3 (each cycle is 42 days)

  4. Dose escalation: Objective response rate (ORR) at each 225Ac dose level during the DLT observation period

    ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per PCWG3 guidelines, as assessed by the Investigator.

    Measured: Up to Cycle 3 (each cycle is 42 days)

  5. Dose escalation: ≥50% decline in Prostate-specific antigen value from baseline (Cycle 1, Day 1) (PSA50) response at each 225Ac dose level during the DLT observation period

    PSA partial response is defined as a ≥50% decline in PSA value from Cycle 1 Day 1 (baseline). This PSA decline must be confirmed to be sustained by a second PSA value obtained 3 to 4 or more weeks later.

    Measured: Up to Cycle 3 (each cycle is 42 days)

  6. Dose expansion: Objective response rate (ORR) by Prostate Cancer Working Group 3 (PCWG3) guidelines based on investigator review

    Measured: Up to 12 months after End of treatment

  7. Dose expansion: ≥50% decline in Prostate-specific antigen value from baseline (Cycle 1, Day 1) (PSA50) response at 12 weeks or later

    Measured: At 12 weeks or later (up to 12 months after End of treatment)

  8. Dose expansion: Best overall Prostate-specific antigen (PSA) response

    Measured: Up to 12 months after End of treatment

Secondary outcomes (11)

  1. Dose escalation & Dose expansion: Radiologic progression-free survival (rPFS ) by PCWG3 based on investigator review

    rPFS is defined as the time from the start of study treatment to the date of first observed disease progression (Investigator's radiological assessment by PCWG3) or death due to any cause, if death occurs before progression is documented.

    Measured: Up to 12 months after end of treatment

  2. Dose escalation & Dose expansion: Duration of PSA50 response

    Duration of PSA50 response by PCWG3 is defined as the time from the first documented PSA partial response as defined above to PSA progression by PCWG3 or death (if death occurs before progression is documented).

    Measured: Up to 12 months after end of treatment

  3. Dose escalation & Dose expansion: Duration of response (DOR) by PCWG3 based on investigator review

    DOR is defined as the time from the first documented objective response of PR or CR by PCWG3, whichever occurs earlier, to disease progression or death (if death occurs before progression is documented).

    Measured: Up to 12 months after end of treatment

  4. Dose escalation: Recommended dose level(s) of 225Ac-pelgi for dose expansion

    Measured: Up to 4 cycles (each cycle is 42 days)

  5. Dose escalation: Recommended dose schedule of 225Ac-pelgi for dose expansion

    Measured: Up to 4 cycles (each cycle is 42 days)

  6. Dose expansion: Recommended dose of 225Ac-pelgi for further clinical development

    Measured: Up to 4 cycles (each cycle is 42 days)

  7. Dose expansion: Recommended dose schedule of 225Ac-pelgi for further clinical development

    Measured: Up to 4 cycles (each cycle is 42 days)

  8. Dose escalation & Dose expansion: Maximum observed concentration (Cmax) of actinium-225

    Measured: Cycle 1, cycle 2 (From Pre-dose up to Day 36 post-dose for each cycle)

  9. Dose escalation & Dose expansion: Maximum observed concentration (Cmax) of total antibody

    Measured: Cycle 1, cycle 2 (From Pre-dose up to Day 36 post-dose for each cycle)

  10. Dose escalation & Dose expansion: Area under the curve (AUC) of actinium-225

    Measured: Cycle 1, cycle 2 (From Pre-dose up to Day 36 post-dose for each cycle)

  11. Dose escalation & Dose expansion: Area under the curve (AUC) of total antibody

    Measured: Cycle 1, cycle 2 (From Pre-dose up to Day 36 post-dose for each cycle)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2023
  2. Study start20 Sep 2023
  3. Primary completion8 Jun 2027 (estimated)
  4. Study completion10 Aug 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
85 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06052306
Sponsor's protocol ID
22143
Other IDs
2022-502623-22-00
Status last verified
30 Sep 2026
First submitted
7 Sep 2023
Last updated
16 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Publications

  • Schatz CA, Zitzmann-Kolbe S, Moen I, Klotz M, Nair S, Stargard S, Bjerke RM, Wickstrom Biseth K, Feng YZ, Indrevoll B, Cruciani V, Karlsson J, Haendler B, Nielsen CH, Alfsen MZ, Hammer S, Hennekes H, Cuthbertson A, Hagemann UB, Larsen A. Preclinical Efficacy of a PSMA-Targeted Actinium-225 Conjugate (225Ac-Macropa-Pelgifatamab): A Targeted Alpha Therapy for Prostate Cancer. Clin Cancer Res. 2024 Jun 3;30(11):2531-2544. doi: 10.1158/1078-0432.CCR-23-3746.

    PubMed 38593212

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BAY3546828 in people with Metastatic Castration-resistant Prostate Cancer, run by Bayer at 11 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Finland, United Kingdom, Canada, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose escalation & Dose expansion: The Incidence of treatment-emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs) (time frame: After first administration of study treatment up to 42 days after the last dose of study treatment). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06052306, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.

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