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)
NCT ID: NCT06052306
Last Updated: 2025-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1
232 participants
INTERVENTIONAL
2023-09-20
2031-08-10
Brief Summary
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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)).
Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Dose expansion group C of BAY3546828
Participants with advanced mCRPC after prior Lutetium-177 labeled PSMA ligand (177Lu-PSMA) treatment.
BAY3546828
Intravenous (IV) infusion on Day 1 of each cycle.
Dose escalation of BAY3546828
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
BAY3546828
Intravenous (IV) infusion on Day 1 of each cycle.
Dose expansion group A of BAY3546828
Participants with advanced mCRPC with at least 1 but no more than 2 prior taxane regimens. No prior radionuclide therapy
BAY3546828
Intravenous (IV) infusion on Day 1 of each cycle.
Dose expansion group B of BAY3546828
Participants with advanced mCRPC who have not received taxane chemotherapy since becoming castration-resistant. No prior radionuclide therapy.
BAY3546828
Intravenous (IV) infusion on Day 1 of each cycle.
Interventions
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BAY3546828
Intravenous (IV) infusion on Day 1 of each cycle.
Eligibility Criteria
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Inclusion Criteria
* 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
* 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).
Exclusion Criteria
* 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.
* 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).
18 Years
MALE
No
Sponsors
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Bayer
INDUSTRY
Responsible Party
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Locations
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City of Hope - Duarte Cancer Center
Duarte, California, United States
M Health Fairview Masonic Cancer Clinic - Clinics and Surgery Center
Minneapolis, Minnesota, United States
XCancer Omaha
Omaha, Nebraska, United States
The University of Texas MD Anderson Cancer Center - Texas Medical Center
Houston, Texas, United States
Utah Cancer Specialists Cancer Center - Medical Oncology
Salt Lake City, Utah, United States
Cross Cancer Institute, Clinical Trials Unit
Edmonton, Alberta, Canada
BC Cancer - Vancouver Site
Vancouver, British Columbia, Canada
Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncology and Hematology
Toronto, Ontario, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, Canada
McGill University Health Centre (MUHC) - Research Institute (RI) - McConnell Centre for Innovative Medicine (CIM)
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke (CHUS) - Hopital Fleurimont
Sherbrooke, Quebec, Canada
Kuopio University Hospital, Kuopion yliopistollinen sairaala (KYS) - Syövänhoitokeskus
Kuopio, Northern Savonia, Finland
HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Syöpäkeskus
Helsinki, Uusimaa, Finland
Docrates Mehiläinen Syöpäsairaala
Helsinki, Uusimaa, Finland
Tampere University Hospital, Tampereen yliopistollinen sairaala (TAYS) - Syöpäkeskus
Tampere, , Finland
CRST Oy - Clinical Research Services Turku
Turku, , Finland
Istituto Europeo di Oncologia s.r.l - Medicina Nucleare
Milan, , Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Medicina Nucleare e Terapia Metabolica
Napoli, , Italy
Universitair Medisch Centrum Groningen
Groningen, , Netherlands
Erasmus Medisch Centrum
Rotterdam, , Netherlands
Sahlgrenska Universitetssjukhuset - Klinisk prövningsenhet Fas I/FIH
Gothenburg, , Sweden
Skånes Universitetssjukhus Lund - Onkologens kliniska forskningsenhet
Lund, , Sweden
Karolinska Universitetssjukhuset - Fas I-enheten Solna CKC
Stockholm, , Sweden
Akademiska Sjukhuset - Fas-I-enheten
Uppsala, , Sweden
Kantonsspital Baden
Baden, Canton of Aargau, Switzerland
Universitätsspital Basel
Basel, Canton of Basel-City, Switzerland
Univestitätsspital Zürich (USZ)
Zurich, , Switzerland
Cambridge University Hospitals NHS Foundation Trust | Addenbrookes Hospital - Clinical Research Centre
Cambridge, Cambridgeshire, United Kingdom
University College London Hospitals NHS Foundation Trust | University College Hospital - NIHR UCLH Clinical Research Facility
London, Greater London, United Kingdom
The Royal Marsden NHS Foundation Trust | Sutton - Oak Foundation Drug Development Unit
Sutton, Surrey, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust | Freeman Hospital - Cancer Trials Research Centre
Newcastle upon Tyne, Tyne and Wear, United Kingdom
Countries
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References
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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.
Related Links
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Other Identifiers
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2022-502623-22-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
22143
Identifier Type: -
Identifier Source: org_study_id