Advanced Metastatic Castration-resistant Prostate CancerPhase 1PAnTHANCT06217822
First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)
A Phase 1 study testing 225Ac-PSMA-Trillium (BAY3563254) in people with Advanced Metastatic Castration-resistant Prostate Cancer and Prostate Specific Membrane Antigen (PSMA) Expression, run by Bayer at 35 sites in 10 countries.
Trial summary
Researchers are looking for a better way to treat participants who have metastatic castration-resistant prostate cancer (mCRPC). mCRPC is a cancer of the prostate (male reproductive gland found below the bladder) that has spread to other parts of the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Metastatic Castration-resistant Prostate Cancer, Prostate Specific Membrane Antigen (PSMA) Expression
- What is being tested?
- 225Ac-PSMA-Trillium (BAY3563254)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 35 sitesin 10 countries
- Study dates
- 7 Mar 2024to 28 May 2032
- 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
- All sexes
- 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
Show all 23Show fewer
- Dose Expansion Group B: Participants must not have received any taxane regimens 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
- Prior treatment with an established Lu-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 treatment 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, as indicated below. Note that blood transfusions (red blood cells or platelets) and administration of G-CSF or GM-CSF are prohibited within 21 days prior to screening for the below bone marrow-related parameters.
- 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 serum creatinine ≤1.5 x ULN
- Participants must have at least one PSMA-positive (prostate-specific membrane antigen) 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, and a minimum starting PSA value of 2.0 ng/mL is mandatory. Progressive mCRPC is 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
- 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)
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) ≥2.5 cm 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 ≥ 1 cm 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 1 cm of enhancing tissue on contrast-enhanced computed 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 treatment, except luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH). Start of study treatment is allowed in shorter timeframes if 5 half-lives of the prior drug(s) have elapsed.
Show all 12Show fewer
- 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, with the exception of prior treatment with radium-223 dichloride more than 3 months before the start of study intervention. Note: Participants who have discontinued radium-223 dichloride treatment due to intolerance are excluded from Groups A and B.
- 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 or radium-223 dichloride 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) v5.0 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.).
Trial locations and contacts
35 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
35 sites in 10 countries
Canada7 sites, 6 recruiting
- Withdrawn
Cross Cancer Institute | Clinical Trials Unit
Edmonton, Alberta, T6G 1Z2
- Recruiting
Juravinski Cancer Centre | Clinical Trials
Hamilton, Ontario, L8V 5C2
- Recruiting
Centre Hospitalier de l'Universite de Montreal (CHUM) | Oncology
Montreal, Quebec, H2X 0C1
- Recruiting
Research Institute of the McGill University Health Centre | McConnell Centre for Innovative Medicine
Montreal, Quebec, H4A 3J1
- Recruiting
Centre hospitalier universitaire de Sherbrooke (CHUS) | Oncology
Sherbrooke, Quebec, J1H 5N4
- Recruiting
Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncology and Hematology
Toronto, Ontario, M5G 2C4
- Recruiting
BC Cancer | Vancouver
Vancouver, British Columbia, V5Z 4E6
Finland5 sites, 4 recruiting
- Recruiting
HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Syöpäkeskus
Helsinki, Uusimaa, 00029
- Recruiting
Docrates Mehiläinen Syöpäsairaala
Helsinki, Uusimaa, 00180
- Recruiting
Kuopio University Hospital, Kuopion yliopistollinen sairaala (KYS) - Syövänhoitokeskus
Kuopio, Northern Savonia, 70210
- Suspended
Tampere University Hospital, Tampereen yliopistollinen sairaala (TAYS) - Syöpäkeskus
Tampere, Pirkanmaa, 33520
- Recruiting
Turku University Hospital, Turun yliopistollinen sairaala (TYKS) - Syöpäkeskus
Turku, Southwest Finland, 20540
United States4 sites, 4 recruiting
- Not yet recruiting
City of Hope - Duarte Cancer Center
Duarte, California, 91010
- Not yet recruiting
The University of Texas MD Anderson Cancer Center - Texas Medical Center
Houston, Texas, 77030
- Not yet recruiting
M Health Fairview Masonic Cancer Clinic - Clinics and Surgery Center
Minneapolis, Minnesota, 55455
- Not yet recruiting
XCancer Omaha
Omaha, Nebraska, 68130
Sweden4 sites, 3 recruiting
- Recruiting
Sahlgrenska Universitetssjukhuset - Sahlgrenska Sjukhuset - Klinisk prövningsenhet Fas I/FIH
Gothenburg, Västra Götaland County, 413 46
- Recruiting
Skånes Universitetssjukhus - Lund - Onkologens kliniska forskningsenhet
Lund, Skåne County, 221 85
- Recruiting
Karolinska Universitetssjukhuset - Solna - Fas I-enheten Solna CKC
Stockholm, Stockholm County, 171 76
- Suspended
Akademiska sjukhuset i Uppsala - Fas 1-enheten
Uppsala, Uppsala County, 751 85
Belgium3 sites, 3 recruiting
- Recruiting
Institut Jules Bordet / Nuclear Medicine
Anderlecht, Brussels Capital, 1070
- Recruiting
AZ Groeninge Campus Kennedylaan - Urology
Kortrijk, West Flanders, 8500
- Not yet recruiting
UZ Leuven - Campus Gasthuisberg - Nuclear Medicine
Leuven, Flemish Brabant, 3000
Switzerland3 sites, 2 recruiting
- Withdrawn
Kantonsspital Baden
Baden, Canton of Aargau, 5404
- Not yet recruiting
Universitätsspital Basel
Basel, Canton of Basel-City, 4056
- Recruiting
UniversitätsSpital Zürich (USZ) - Klinik für Medizinische Onkologie und Hämatologie
Zurich, 8091
United Kingdom3 sites, 3 recruiting
- Recruiting
University College London Hospitals NHS Foundation Trust | University College Hospital - NIHR UCLH Clinical Research Facility
London, Greater London, W1T 7HA
- Not yet recruiting
The Newcastle upon Tyne Hospitals NHS Foundation Trust | Freeman Hospital - Cancer Trials Research Centre
Newcastle upon Tyne, Tyne and Wear, NE7 7DN
- Recruiting
The Royal Marsden NHS Foundation Trust | Sutton - Oak Foundation Drug Development Unit
Sutton, Surrey, SM2 5PT
Italy2 sites, 2 recruiting
- Recruiting
Istituto Europeo di Oncologia s.r.l - Medicina Nucleare
Milan, 20141
- Not yet recruiting
IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Medicina Nucleare e Terapia Metabolica
Naples, 80131
Japan2 sites, 2 recruiting
- Not yet recruiting
The Cancer Institute Hospital of JFCR
Koto-ku, Tokyo, 135-8550
- Not yet recruiting
Yokohama City University Hospital
Yokohama, Kanagawa, 236-0004
Netherlands2 sites, 1 recruiting
- Recruiting
Universitair Medisch Centrum Groningen (UMCG) - UMC Groningen Comprehensive Cancer Center
Groningen, 9713 GZ
- Withdrawn
Erasmus Medisch Centrum
Rotterdam, South Holland, 3015 CE
About this study
Official title: A Phase 1 Open-label, First-in-human, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of 225Ac-PSMA-Trillium in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)
Researchers are looking for a better way to treat participants who have metastatic castration-resistant prostate cancer (mCRPC).
mCRPC is a cancer of the prostate (male reproductive gland found below the bladder) that has spread to other parts of the body. This type of prostate cancer does not respond to hormone treatment used to lower the level of testosterone, a male sex hormone, to prevent cancer from growing.
Read more
The study treatment 225Ac-PSMA-Trillium, also called BAY3563254, is under development to treat advanced metastatic castration-resistant prostate cancer. It works by binding to PSMA and giving off radiation that can damage cancer cells and stop them from growing.
The main purpose of this first-in-human study is to learn:
- How safe is BAY3563254 in participants.
- What is the recommended dose of BAY3563254 that is safe and works well that will be further tested in Part 2 of the study.
- How well does BAY3563254 work in participants.
To answer this, the researchers will look at:
- The number and severity of medical problems including serious medical problems that participants experience after taking BAY3563254
- The number of dose-limiting toxicities (DLT) at each dose level. A DLT is a medical problem caused by a drug that is too severe to continue the use of that specific dose.
- The number of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR))
- The number of participants who have a decrease in the levels of PSA* by at least 50% in their blood (also known as PSA50). PSA is a protein made by the prostate gland. High levels of PSA may indicate the presence of prostate cancer.
- Participants' best response to treatment based on their PSA levels (also known as the best overall PSA response).
The study will have two parts. The first part, called dose escalation, is done to find the most appropriate dose of BAY3563254 for use in the second part of the study. For this, each participant will receive one of different increasing amounts of BAY3563254. They will take BAY3563254 as an injection into a vein. All participants in the second part of the study, called dose expansion, will receive the most appropriate dose of BAY3563254 that was identified from the first part of the study.
Participants in this study will take the study treatment once every 6 or 8 weeks, which is known as a treatment cycle. Each participant will have up to 4 of these treatment cycles, if the participant benefits from the treatment. Each participant will be in the study for approximately 6 years, including a screening phase of up to 30 days, 6 months of treatment depending on the participant's benefit, and a follow up phase of 60 months after the end of treatment.
In addition, substudies performed during both dose escalation and dose expansion parts of the study will evaluate:
- the clearance of radioactivity from the body over time
- the doses of radiation that are delivered to normal organs and tumors
During the study, the doctors and their study team will:
- take blood and urine samples
- check vital signs such as blood pressure, heart rate, and body temperature
- examine heart health using electrocardiogram (ECG)
- take tumor samples if required
- check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and bone scan
- check the tumor status using PET (positron emission tomography)
- check the amount of radiation absorbed by tumors and normal organs using SPECT/CT (single-photon emission tomography and computed tomography scan)
- ask the participants questions about how they are feeling and what adverse events they are having.
An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study.
The treatment period ends with a visit in 6-12 weeks after the last BAY3563254 dose. About 6-12 weeks after the last dose and every 6 weeks thereafter, the study doctors and their team will check the participants' health and any changes in their cancer. This active follow-up period ends after 18 months. The long-term follow-up period will start after the end of the active follow-up visit and will continue for up to 60 months after the the last BAY3563254 dose. Participants will be contacted, typically by phone call or clinic visit, approximately every 12 weeks after the end of active follow-up.
- Conditions
- Advanced Metastatic Castration-resistant Prostate Cancer, Prostate Specific Membrane Antigen (PSMA) Expression
- Being tested
- 225Ac-PSMA-Trillium (BAY3563254)
- Keywords
- mCRPC, PSMA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
225Ac-PSMA-Trillium (BAY3563254)Drug
Intravenous slow injection on Day 1 of a 6 week treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation of BAY3563254 | Experimental | Participants with advanced mCRPC will receive increased 225Ac-PSMA-Trillium doses in a planned stepwise fashion. Receives: Drug: 225Ac-PSMA-Trillium (BAY3563254) |
| Dose expansion group A of BAY3563254 | Experimental | Participants with advanced mCRPC must have received at least 1 but no more than 2 prior taxane-based chemotherapy regimens. No prior treatment with 177Lu-PSMA. Receives: Drug: 225Ac-PSMA-Trillium (BAY3563254) |
| Dose expansion group B of BAY3563254 | Experimental | Participants with advanced mCRPC must *not* have received taxane-based chemotherapy since becoming castration resistant. No prior treatment with 177Lu-PSMA. Receives: Drug: 225Ac-PSMA-Trillium (BAY3563254) |
| Dose expansion group C of BAY3563254 | Experimental | Participants with advanced mCRPC treated with 225Ac-PSMA-Trillium, who have received treatment with an established 177Lu-PSMA therapy and who did not discontinue 177Lu-PSMA treatment due to intolerance. Receives: Drug: 225Ac-PSMA-Trillium (BAY3563254) |
| 225Ac-PSMA-Trillium Imaging and Dosimetry | Experimental | 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. Receives: Drug: 225Ac-PSMA-Trillium (BAY3563254) |
| HPGe or NaI Whole Body Radioactivity Measurement of 225Ac-PSMA-Trillium | Experimental | 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. Receives: Drug: 225Ac-PSMA-Trillium (BAY3563254) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation and Dose Expansion: Incidence of TEAEs (including TESAEs)
TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event
Measured: After the first administration of study intervention up to 42 days after the last dose of study intervention
Dose Escalation and Dose Expansion: Severity of TEAEs (including TESAEs)
Measured: After the first administration of study intervention up to 42 days after the last dose of study intervention
Dose Escalation: Incidence of DLTs
DLT: Dose-Limiting Toxicities
Measured: Up to and including Cycle 3 (each cycle is 42 days)
Dose Escalation and Dose Expansion: ORR by PCWG3 guideline based on Investigator review
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 18 months after end of treatment
Dose Escalation and Dose Expansion: PSA50 response
PSA50 response is defined as a ≥50% decline in PSA value from baseline (Cycle 1 Day 1).
Measured: At 12 weeks or later (up to 18 months after end of treatment)
Dose Expansion: Best overall PSA response
Best overall PSA response corresponds to the maximum percentage decline or the minimum percentage increase (if no decline) in PSA value from baseline (Cycle 1 Day 1).
Measured: Up to 18 months after end of treatment
Secondary outcomes (9)
Dose Expansion: Recommended dose for further clinical development
Measured: Up to 18 months after end of treatment
Dose Expansion: Recommended dose regimen for further clinical development
Measured: Up to 18 months after end of treatment
Dose Escalation and 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 without progression is documented.
Measured: Up to 18 months after end of treatment
Dose Escalation and 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 without progression is documented).
Measured: Up to 18 months after end of treatment
Dose Escalation and Dose Expansion: Duration of PSA50 response
Duration of PSA50 response is defined as the time from the first documented PSA50 response to PSA progression by PCWG3 or death (if death occurs without progression is documented).
Measured: Up to 18 months after end of treatment
Dose Escalation and Dose Expansion: Cmax of 225Ac
Measured: Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle)
Dose Escalation and Dose Expansion: AUC and AUC(0-tlast) of 225Ac
Measured: Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle)
Dose Escalation and Dose Expansion: Cmax of PSMA-Trillium-macropa peptide
Measured: Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle)
Dose Escalation and Dose Expansion: AUC and AUC(0-tlast) of PSMA-Trillium-macropa peptide
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.
- First posted23 Jan 2024
- Study start7 Mar 2024
- Primary completion26 Nov 2028 (estimated)
- Study completion28 May 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 198 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06217822
- Sponsor's protocol ID
- 22049
- Other IDs
- 2023-507486-26-00, 2023
- Acronym
- PAnTHA
- Status last verified
- Jul 2026
- First submitted
- 19 Dec 2023
- Last updated
- 7 Jul 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.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-label, First-in-human, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of 225Ac-PSMA-Trillium in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)
- ClinicalTrials.gov ID
- NCT06217822
- Acronym / sponsor ID
- PAnTHA / 22049
- Conditions
- Advanced Metastatic Castration-resistant Prostate Cancer, Prostate Specific Membrane Antigen (PSMA) Expression
- Keywords
- mCRPC, PSMA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 198 participants (estimated)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 7 Mar 2024 (actual)
- Primary completion
- 26 Nov 2028 (estimated)
- Study completion
- 28 May 2032 (estimated)
- First posted
- 23 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Researchers are looking for a better way to treat participants who have metastatic castration-resistant prostate cancer (mCRPC).
mCRPC is a cancer of the prostate (male reproductive gland found below the bladder) that has spread to other parts of the body. This type of prostate cancer does not respond to hormone treatment used to lower the level of testosterone, a male sex hormone, to prevent cancer from growing.
The study treatment 225Ac-PSMA-Trillium, also called BAY3563254, is under development to treat advanced metastatic castration-resistant prostate cancer. It works by binding to PSMA and giving off radiation that can damage cancer cells and stop them from growing.
The main purpose of this first-in-human study is to learn:
- How safe is BAY3563254 in participants.
- What is the recommended dose of BAY3563254 that is safe and works well that will be further tested in Part 2 of the study.
- How well does BAY3563254 work in participants.
To answer this, the researchers will look at:
- The number and severity of medical problems including serious medical problems that participants experience after taking BAY3563254
- The number of dose-limiting toxicities (DLT) at each dose level. A DLT is a medical problem caused by a drug that is too severe to continue the use of that specific dose.
- The number of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR))
- The number of participants who have a decrease in the levels of PSA* by at least 50% in their blood (also known as PSA50). PSA is a protein made by the prostate gland. High levels of PSA may indicate the presence of prostate cancer.
- Participants' best response to treatment based on their PSA levels (also known as the best overall PSA response).
The study will have two parts. The first part, called dose escalation, is done to find the most appropriate dose of BAY3563254 for use in the second part of the study. For this, each participant will receive one of different increasing amounts of BAY3563254. They will take BAY3563254 as an injection into a vein. All participants in the second part of the study, called dose expansion, will receive the most appropriate dose of BAY3563254 that was identified from the first part of the study.
Participants in this study will take the study treatment once every 6 or 8 weeks, which is known as a treatment cycle. Each participant will have up to 4 of these treatment cycles, if the participant benefits from the treatment. Each participant will be in the study for approximately 6 years, including a screening phase of up to 30 days, 6 months of treatment depending on the participant's benefit, and a follow up phase of 60 months after the end of treatment.
In addition, substudies performed during both dose escalation and dose expansion parts of the study will evaluate:
- the clearance of radioactivity from the body over time
- the doses of radiation that are delivered to normal organs and tumors
During the study, the doctors and their study team will:
- take blood and urine samples
- check vital signs such as blood pressure, heart rate, and body temperature
- examine heart health using electrocardiogram (ECG)
- take tumor samples if required
- check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and bone scan
- check the tumor status using PET (positron emission tomography)
- check the amount of radiation absorbed by tumors and normal organs using SPECT/CT (single-photon emission tomography and computed tomography scan)
- ask the participants questions about how they are feeling and what adverse events they are having.
An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study.
The treatment period ends with a visit in 6-12 weeks after the last BAY3563254 dose. About 6-12 weeks after the last dose and every 6 weeks thereafter, the study doctors and their team will check the participants' health and any changes in their cancer. This active follow-up period ends after 18 months. The long-term follow-up period will start after the end of the active follow-up visit and will continue for up to 60 months after the the last BAY3563254 dose. Participants will be contacted, typically by phone call or clinic visit, approximately every 12 weeks after the end of active follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose escalation of BAY3563254 | Experimental | Drug: 225Ac-PSMA-Trillium (BAY3563254)Participants with advanced mCRPC will receive increased 225Ac-PSMA-Trillium doses in a planned stepwise fashion. |
| Dose expansion group A of BAY3563254 | Experimental | Drug: 225Ac-PSMA-Trillium (BAY3563254)Participants with advanced mCRPC must have received at least 1 but no more than 2 prior taxane-based chemotherapy regimens. No prior treatment with 177Lu-PSMA. |
| Dose expansion group B of BAY3563254 | Experimental | Drug: 225Ac-PSMA-Trillium (BAY3563254)Participants with advanced mCRPC must *not* have received taxane-based chemotherapy since becoming castration resistant. No prior treatment with 177Lu-PSMA. |
| Dose expansion group C of BAY3563254 | Experimental | Drug: 225Ac-PSMA-Trillium (BAY3563254)Participants with advanced mCRPC treated with 225Ac-PSMA-Trillium, who have received treatment with an established 177Lu-PSMA therapy and who did not discontinue 177Lu-PSMA treatment due to intolerance. |
| 225Ac-PSMA-Trillium Imaging and Dosimetry | Experimental | Drug: 225Ac-PSMA-Trillium (BAY3563254)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. |
| HPGe or NaI Whole Body Radioactivity Measurement of 225Ac-PSMA-Trillium | Experimental | Drug: 225Ac-PSMA-Trillium (BAY3563254)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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 Expansion Group B: Participants must not have received any taxane regimens since becoming castration-resistant
Key exclusion criteria (12 listed)
- 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.
- Prior systemic anticancer therapy including chemotherapy, NAAD, biologic therapy, immunotherapy, or investigational therapies within 4 weeks of the start of study treatment, except luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH). Start of study treatment is allowed in shorter timeframes if 5 half-lives of the prior drug(s) have elapsed.
- Prior radiopharmaceutical treatment using actinium-225.
- Dose escalation and Dose expansion Groups A and B: Prior treatment with a radiopharmaceutical is prohibited, with the exception of prior treatment with radium-223 dichloride more than 3 months before the start of study intervention. Note: Participants who have discontinued radium-223 dichloride treatment due to intolerance are excluded from Groups A and B.
- 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 or radium-223 dichloride treatment due to intolerance are excluded from Group C.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 225Ac-PSMA-Trillium (BAY3563254)Intravenous slow injection on Day 1 of a 6 week treatment cycle. | Drug | 225Ac-PSMA-Trillium Imaging and Dosimetry, Dose escalation of BAY3563254, Dose expansion group A of BAY3563254, Dose expansion group B of BAY3563254, Dose expansion group C of BAY3563254, HPGe or NaI Whole Body Radioactivity Measurement of 225Ac-PSMA-Trillium |
Primary outcome
Dose Escalation and Dose Expansion: Incidence of TEAEs (including TESAEs)
Time frame: After the first administration of study intervention up to 42 days after the last dose of study intervention
TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event
Dose Escalation and Dose Expansion: Severity of TEAEs (including TESAEs)
Time frame: After the first administration of study intervention up to 42 days after the last dose of study intervention
Dose Escalation: Incidence of DLTs
Time frame: Up to and including Cycle 3 (each cycle is 42 days)
DLT: Dose-Limiting Toxicities
Dose Escalation and Dose Expansion: ORR by PCWG3 guideline based on Investigator review
Time frame: Up to 18 months after end of treatment
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.
Dose Escalation and Dose Expansion: PSA50 response
Time frame: At 12 weeks or later (up to 18 months after end of treatment)
PSA50 response is defined as a ≥50% decline in PSA value from baseline (Cycle 1 Day 1).
Dose Expansion: Best overall PSA response
Time frame: Up to 18 months after end of treatment
Best overall PSA response corresponds to the maximum percentage decline or the minimum percentage increase (if no decline) in PSA value from baseline (Cycle 1 Day 1).
9 secondary outcomes
Dose Expansion: Recommended dose for further clinical development
Time frame: Up to 18 months after end of treatment
Dose Expansion: Recommended dose regimen for further clinical development
Time frame: Up to 18 months after end of treatment
Dose Escalation and Dose Expansion: Radiologic progression-free survival (rPFS) by PCWG3 based on Investigator review
Time frame: Up to 18 months after end of treatment
Dose Escalation and Dose Expansion: Duration of response (DOR) by PCWG3 based on Investigator review
Time frame: Up to 18 months after end of treatment
Dose Escalation and Dose Expansion: Duration of PSA50 response
Time frame: Up to 18 months after end of treatment
Dose Escalation and Dose Expansion: Cmax of 225Ac
Time frame: Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle)
Dose Escalation and Dose Expansion: AUC and AUC(0-tlast) of 225Ac
Time frame: Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle)
Dose Escalation and Dose Expansion: Cmax of PSMA-Trillium-macropa peptide
Time frame: Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle)
Dose Escalation and Dose Expansion: AUC and AUC(0-tlast) of PSMA-Trillium-macropa peptide
Time frame: Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.Link provided by the sponsor.
- Individual participant dataSharing planned: 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.
Related trials for Advanced Metastatic Castration-resistant Prostate Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Active, not recruitingPhase 2
Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
Enrolling by invitationPhase 1
A Study of ITC-6146RO in Patients With Advanced or Metastatic Cancer Who Have Failed Standard Therapy
Metastatic Castration-resistant Prostate Cancer, Non-small Cell Lung Cancer
RecruitingPhase 3
A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1)
Metastatic Castration Resistant Prostate Cancer
Active, not recruitingPhase 1
A Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer
Prostatic Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
35 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 225Ac-PSMA-Trillium (BAY3563254) in people with Advanced Metastatic Castration-resistant Prostate Cancer and Prostate Specific Membrane Antigen (PSMA) Expression, run by Bayer at 35 sites in 10 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 23 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Canada, Finland, United States, Sweden, Belgium and 5 more countries. 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?
Contact Bayer Clinical Trials Contact ((+)1-888-84 22937, clinical-trials-contact@bayer.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation and Dose Expansion: Incidence of TEAEs (including TESAEs) (time frame: After the first administration of study intervention up to 42 days after the last dose of study intervention). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jul 2026.