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Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Taxane

Radiopharmaceuticals

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

Participants with advanced mCRPC treated with 225Ac-PSMA-Trillium, who must have received at least 1 but no more than 2 prior taxane-based chemotherapy regimens. Prior radiopharmaceutical treatment is not permitted.

Participants with advanced mCRPC treated with 225Ac-PSMA-Trillium, who must not have received taxane-based chemotherapy since becoming castration resistant. Prior radiopharmaceutical treatment is not permitted.

Participants with advanced mCRPC treated with 225Ac-PSMA-Trillium, who must have had prior treatment with 177Lu-PSMA more than 6 weeks before the start of study treatment and at least 1 but no more than 2 taxane regimens (or been deemed ineligible for or refused taxane therapy on consultation with their physician).

Participants who sign informed consents for both the main study and the optional 111In-PSMA-Trillium and Tris-POC Imaging Substudy. 111In-PSMA-Trillium and Tris-POC Imaging Substudy participants are not eligible for the 225Ac-PSMA-Trillium Imaging and Dosimetry Substudy or for the dense-PK sub-cohort in dose expansion. Each substudy participant will enter the 111In-PSMA-Trillium and Tris-POC Imaging Substudy period after completing a shortened screening period and before starting study treatment with 225Ac-PSMA-Trillium.

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 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.

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

225Ac-PSMA-Trillium (BAY3563254)

0.5 mg/mL (7.5 mg/vial), i.v slow injection, Tris-POC will be administered approximately 15 minutes prior to the second dose of the 111In-PSMA-Trillium imaging agent.

Tris-POC (BAY2688901)

111In dose of 185 MBq (5 mCi) ± 10% and PSMA-Trillium-DOTA peptide dose of approximately 0.05 to 0.08 mg (approximately 0.04 mg if dosed the day after manufacture), slow intravenous injection bolus followed by 10 mL flush of normal saline

111In-PSMA-Trillium (BAY3632687)

Bayer Clinical Trials Contact

Researchers are looking for a better way to treat men 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 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
* the ability of an experimental agent (Tris-POC) to decrease the amount of radiation absorbed by normal organs.

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.

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

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)

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.

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

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.

PSA50 response is defined as a ≥50% decline in PSA value from baseline (Cycle 1 Day 1).

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).

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.

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).

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).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)	NCT06217822	Advanced Metast... Prostate Specif...	225Ac-PSMA-Tril... Tris-POC (BAY26... 111In-PSMA-Tril...	18 Years -	Bayer
First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)	NCT06217822	Advanced Metast... Prostate Specif...	225Ac-PSMA-Tril... Tris-POC (BAY26... 111In-PSMA-Tril...	18 Years -	Bayer

Spots Global Cancer Trial Database for prostate specific membrane antigen (psma) expression