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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 225Ac-PSMA-Trillium (BAY3563254) — DRUG
  Intravenous slow injection on Day 1 of a 6 week treatment cycle.

Study Details

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.

Key Dates

Start date

Mar 7, 2024

Status verified

Apr 2026

Primary completion

Nov 26, 2028

Completion

May 28, 2032

Study Design

Enrollment

198 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Dose escalation of BAY3563254
  Participants with advanced mCRPC will receive increased 225Ac-PSMA-Trillium doses in a planned stepwise fashion.
• Experimental: Dose expansion group A of 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.
• Experimental: Dose expansion group B of BAY3563254
  Participants with advanced mCRPC must \*not\* have received taxane-based chemotherapy since becoming castration resistant. No prior treatment with 177Lu-PSMA.
• Experimental: Dose expansion group C of 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.
• Experimental: 225Ac-PSMA-Trillium Imaging and Dosimetry
  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.
• Experimental: HPGe or NaI Whole Body Radioactivity Measurement of 225Ac-PSMA-Trillium
  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.

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 ]

Central Contacts

• Bayer Clinical Trials Contact
  (+)1-888-84 22937
  [email protected]

Locations (4)

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