First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)

NCT06217822 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 220492023-507486-26-00
• Study Type: interventional
• Target: 198
• Locations: 10 countries
• Sites: 35

Brief 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. 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.

Conditions

Prostate Specific Membrane Antigen (PSMA) Expression; Advanced Metastatic Castration-resistant Prostate Cancer

Keywords

mCRPC; PSMA

Outcome Measures

Primary Outcomes (6)

• Dose Escalation and Dose Expansion: Incidence of TEAEs (including TESAEs)

  TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event

  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)

  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

  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.

  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).

  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).

  Up to 18 months after end of treatment

Secondary Outcomes (9)

• Dose Expansion: Recommended dose for further clinical development

  Up to 18 months after end of treatment

• Dose Expansion: Recommended dose regimen for further clinical development

  Up to 18 months after end of treatment

• Dose Escalation and Dose Expansion: Radiologic progression-free survival (rPFS) by PCWG3 based on Investigator review

  Up to 18 months after end of treatment

• Dose Escalation and Dose Expansion: Duration of response (DOR) by PCWG3 based on Investigator review

  Up to 18 months after end of treatment

• Dose Escalation and Dose Expansion: Duration of PSA50 response

  Up to 18 months after end of treatment

Study Arms (6)

Dose escalation of BAY3563254

EXPERIMENTAL

Participants with advanced mCRPC will receive increased 225Ac-PSMA-Trillium doses in a planned stepwise fashion.

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.

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.

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.

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.

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.

Drug: 225Ac-PSMA-Trillium (BAY3563254)

Interventions

225Ac-PSMA-Trillium (BAY3563254) DRUG

Intravenous slow injection on Day 1 of a 6 week treatment cycle.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (35)

City of Hope - Duarte Cancer Center

Duarte, California, 91010, United States

NOT YET RECRUITING

M Health Fairview Masonic Cancer Clinic - Clinics and Surgery Center

Minneapolis, Minnesota, 55455, United States

NOT YET RECRUITING

XCancer Omaha

Omaha, Nebraska, 68130, United States

NOT YET RECRUITING

The University of Texas MD Anderson Cancer Center - Texas Medical Center

Houston, Texas, 77030, United States

NOT YET RECRUITING

Institut Jules Bordet / Nuclear Medicine

Anderlecht, 1070, Belgium

RECRUITING

AZ Groeninge Campus Kennedylaan - Urology

Kortrijk, 8500, Belgium

RECRUITING

UZ Leuven - Campus Gasthuisberg - Nuclear Medicine

Leuven, 3000, Belgium

NOT YET RECRUITING

Cross Cancer Institute | Clinical Trials Unit

Edmonton, Alberta, T6G 1Z2, Canada

WITHDRAWN

BC Cancer | Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Juravinski Cancer Centre | Clinical Trials

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncology and Hematology

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

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

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

McGill University Health Centre (MUHC) - Research Institute (RI) - McConnell Centre for Innovative Medicine (CIM)

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Centre hospitalier universitaire de Sherbrooke (CHUS) | Oncology

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

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

Kuopio, Northern Savonia, 70210, Finland

RECRUITING

Tampere University Hospital, Tampereen yliopistollinen sairaala (TAYS) - Syöpäkeskus

Tampere, Pirkanmaa, 33520, Finland

SUSPENDED

Turku University Hospital, Turun yliopistollinen sairaala (TYKS) - Syöpäkeskus

Turku, Southwest Finland, 20540, Finland

RECRUITING

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

Helsinki, Uusimaa, 00029, Finland

RECRUITING

Docrates Mehiläinen Syöpäsairaala

Helsinki, Uusimaa, 00180, Finland

NOT YET RECRUITING

Istituto Europeo di Oncologia s.r.l - Medicina Nucleare

Milan, 20141, Italy

RECRUITING

IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Medicina Nucleare e Terapia Metabolica

Naples, 80131, Italy

NOT YET RECRUITING

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

NOT YET RECRUITING

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

NOT YET RECRUITING

Erasmus Medisch Centrum

Rotterdam, South Holland, 3015 CE, Netherlands

WITHDRAWN

Universitair Medisch Centrum Groningen (UMCG) - UMC Groningen Comprehensive Cancer Center

Groningen, 9713 GZ, Netherlands

RECRUITING

Skånes Universitetssjukhus Lund - Onkologens kliniska forskningsenhet

Lund, Skåne County, 221 85, Sweden

RECRUITING

Karolinska Universitetssjukhuset - Fas I-enheten Solna CKC

Stockholm, Stockholm County, 171 76, Sweden

RECRUITING

Akademiska sjukhuset i Uppsala - Fas 1-enheten

Uppsala, Uppsala County, 751 85, Sweden

SUSPENDED

Sahlgrenska Universitetssjukhuset - Klinisk prövningsenhet Fas I/FIH

Gothenburg, Västra Götaland County, 413 46, Sweden

RECRUITING

Kantonsspital Baden

Baden, Canton of Aargau, 5404, Switzerland

WITHDRAWN

Universitätsspital Basel

Basel, Canton of Basel-City, 4056, Switzerland

NOT YET RECRUITING

Univestitätsspital Zürich (USZ)

Zurich, 8091, Switzerland

RECRUITING

University College London Hospitals NHS Foundation Trust | University College Hospital - NIHR UCLH Clinical Research Facility

London, Greater London, W1T 7HA, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust | Sutton - Oak Foundation Drug Development Unit

Sutton, Surrey, SM2 5PT, United Kingdom

ACTIVE NOT RECRUITING

The Newcastle upon Tyne Hospitals NHS Foundation Trust | Freeman Hospital - Cancer Trials Research Centre

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

NOT YET RECRUITING

Central Study Contacts

Bayer Clinical Trials Contact

CONTACT

(+)1-888-84 22937; clinical-trials-contact@bayer.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 23, 2024
• Study Start: March 7, 2024
• Primary Completion (Estimated): November 26, 2028
• Study Completion (Estimated): May 28, 2032
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (4); GB (3); CA (7); BE (3); IT (2); JP (2); NL (2); CH (3); FI (5); US (4)