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.
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).
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
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.
Sequential
225Ac-PSMA-Trillium (BAY3563254)
DrugIntravenous slow injection on Day 1 of a 6 week treatment cycle.
6
Treatment groupsSee each treatment group below.
Dose Escalation and Dose Expansion: Incidence of TEAEs (including TESAEs)
TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event
Dose Escalation and Dose Expansion: Severity of TEAEs (including TESAEs)
Dose Escalation: Incidence of DLTs
DLT: Dose-Limiting Toxicities
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.
Dose Expansion: Recommended dose for further clinical development
Dose Expansion: Recommended dose regimen for further clinical development
Dose Escalation and Dose Expansion: Radiologic progression-free survival (rPFS) by PCWG3 based on Investigator review
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.
Dose Escalation and Dose Expansion: Duration of response (DOR) by PCWG3 based on Investigator review
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).
