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225Ac-PSMA-Trillium

Phase 1

Advanced Metastatic Castration-resistant Prostate Cancer | Small molecule | Oncology |Bayer AG|Last Updated: Jul 7, 2026

Target and mechanism

ModalitySmall molecule

Also known as 225Ac-PSMA-Trillium (BAY3563254)

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment198

FDA Designations

No designations recorded

Clinical trial landscape

225Ac-PSMA-Trillium · 1 trial · 2 indications

Phase 1 1
NCT06217822First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)Advanced Metastatic Castration-resistant Prostate Cancer
RECRUITING198 Analytics
PHASE1RECRUITING
First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)
Advanced Metastatic Castration-resistant Prostate CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

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 DLTs
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
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
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
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).

Secondary Endpoints

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
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Dose escalation of BAY3563254EXPERIMENTALParticipants with advanced mCRPC will receive increased 225Ac-PSMA-Trillium doses in a planned stepwise fashion.
Dose expansion group A of BAY3563254EXPERIMENTALParticipants 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 BAY3563254EXPERIMENTALParticipants 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 BAY3563254EXPERIMENTALParticipants 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 DosimetryEXPERIMENTALThe 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-TrilliumEXPERIMENTALHPGe 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.

Interventions

NameTypeDescription
225Ac-PSMA-Trillium (BAY3563254)DRUGIntravenous slow injection on Day 1 of a 6 week treatment cycle.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites35

Inclusion Criteria: * 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 and...

Countries:United StatesBelgiumCanadaFinlandItalyJapanNetherlandsSwedenSwitzerlandUnited Kingdom
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Recent Changes (Last 90 Days)

LOWJul 7, 2026NCT06217822lastUpdatePostDate: changed
LOWJul 7, 2026NCT06217822lastUpdatePostDate: changed

Frequently asked questions about 225Ac-PSMA-Trillium

What is 225Ac-PSMA-Trillium used for?

225Ac-PSMA-Trillium is an investigational small molecule being developed for advanced metastatic castration-resistant prostate cancer (mCRPC). It is a targeted radionuclide therapy designed to deliver actinium-225 to prostate-specific membrane antigen (PSMA) expressing tumor cells. The drug is currently in Phase 1 clinical development and is not yet approved by regulatory authorities.

What does 225Ac-PSMA-Trillium target?

225Ac-PSMA-Trillium targets prostate-specific membrane antigen (PSMA), a protein highly expressed on prostate cancer cells. The drug is a small molecule conjugated to the radioisotope actinium-225, which allows targeted delivery of radiation to PSMA-positive tumors. This mechanism is being evaluated in patients with advanced metastatic castration-resistant prostate cancer.

Who makes 225Ac-PSMA-Trillium?

225Ac-PSMA-Trillium is being developed by Bayer AG, a multinational pharmaceutical company headquartered in Germany. Bayer's stock is traded over-the-counter under the ticker BAYRY. The company is conducting a first-in-human Phase 1 study of this investigational therapy for advanced metastatic castration-resistant prostate cancer.

What phase is 225Ac-PSMA-Trillium in?

225Ac-PSMA-Trillium is in Phase 1 clinical development. It is an investigational drug and has not received regulatory approval. The ongoing Phase 1 trial is a first-in-human study designed to evaluate the safety, tolerability, and preliminary efficacy of the drug in patients with advanced metastatic castration-resistant prostate cancer.

What clinical trials is 225Ac-PSMA-Trillium in?

225Ac-PSMA-Trillium is being studied in a single Phase 1 clinical trial registered as NCT06217822. This first-in-human study is recruiting 198 participants with advanced metastatic castration-resistant prostate cancer and PSMA expression. The trial is active and enrolling patients across multiple countries including the United States, Belgium, Canada, Finland, Italy, Japan, Netherlands, Sweden, Switzerland, and the United Kingdom.

Is 225Ac-PSMA-Trillium the same as BAY3563254?

Yes, 225Ac-PSMA-Trillium is also known as BAY3563254. Both names refer to the same investigational drug being developed by Bayer AG for advanced metastatic castration-resistant prostate cancer. The drug is a small molecule radionuclide therapy targeting PSMA and is currently in Phase 1 clinical trials.