Study of 225Ac-PSMA-Trillium for Advanced Prostate Cancer
This study is testing a new treatment called 225Ac-PSMA-Trillium (also known as BAY3563254) for people with advanced metastatic castration-resistant prostate cancer (mCRPC). This is a type of prostate cancer that has spread and no longer responds to standard hormone therapy. The treatment works by targeting a protein called PSMA on cancer cells and delivering radiation to damage them. The main goal of this first-in-human study is to understand how safe 225Ac-PSMA-Trillium is. You may be able to join if you have mCRPC that has been confirmed by a doctor, have had certain prior treatments, and have low testosterone levels. The study aims to enroll 198 participants.
- Study design
- This is an interventional study, meaning participants will receive a specific treatment. It is a 'first-in-human' study, focusing on safety, and plans to enroll 198 participants.
- What's involved
- You would receive 225Ac-PSMA-Trillium as an intravenous (into a vein) slow injection on Day 1 of a 6-week treatment cycle.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your safety will be monitored from the first administration of the study treatment up to 42 days after your last dose.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06217822
First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)
Recruiting
PHASE1Ages 18+InterventionalTreatmentBayer
~198 participants
Updated 2026-07-07 on ClinicalTrials.gov
What's tested:225Ac-PSMA-Trillium (BAY3563254)
At a glance
Recruiting sites
20 of 35 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Dose Escalation and Dose Expansion: Incidence of TEAEs (including TESAEs)
Measured over After the first administration of study intervention up to 42 days after the last dose of study intervention
+5 more outcomes measured
Conditions
Where it's being run
35 sites across 30 statesQuebec3
Ontario2
Uusimaa2
Italy2
California1
Minnesota1
Nebraska1
Texas1
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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).
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:
Exclusion
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.
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.
What this trial measures
- Dose Escalation and Dose Expansion: Incidence of TEAEs (including TESAEs)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)After the first administration of study intervention up to 42 days after the last dose of study intervention
- Dose Escalation: Incidence of DLTsUp 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 reviewUp 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 responseAt 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 responseUp 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).