A Study to Learn How Safe the Study Treatment Actinium-225-macropa-pelgifatamab (BAY3546828) is, How it Affects the Body, How it Moves Into, Through and Out of the Body, and About Its Anticancer Activity in Men With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC) - Trial NCT06052306

Timeline & Enrollment

Primary Outcome

Dose escalation & Dose expansion: The Incidence of treatment-emergent adverse events (TEAEs) including treatment-emergent serious adverse events (TESAEs),Dose escalation & Dose expansion: The Severity of TEAEs including TESAEs,Dose escalation: Incidence of dose limiting toxicities (DLTs) at each 225Ac dose level during the DLT observation period,Dose escalation: Objective response rate (ORR) at each 225Ac dose level during the DLT observation period,Dose escalation: ≥50% decline in Prostate-specific antigen value from baseline (Cycle 1, Day 1) (PSA50) response at each 225Ac dose level during the DLT observation period,Dose expansion: Objective response rate (ORR) by Prostate Cancer Working Group 3 (PCWG3) guidelines based on investigator review,Dose expansion: ≥50% decline in Prostate-specific antigen value from baseline (Cycle 1, Day 1) (PSA50) response at 12 weeks or later,Dose expansion: Best overall Prostate-specific antigen (PSA) response

Summary

Researchers are looking for a better way to treat people who have advanced metastatic
 castration-resistant prostate cancer (mCRPC). In men with metastatic castration-resistant
 prostate cancer (mCRPC), the cancer of the prostate has spread to other parts of the body
 (metastatic) and does not respond to the lowering of testosterone levels in the body
 (castration resistant). The cancer is 'advanced' and is unlikely to be cured or controlled
 with currently available treatments. Despite new treatment options for men with prostate
 cancer in recent years, the cancer often returns and worsens.
 
 The study treatment actinium-225-macropa-pelgifatamab (also called 225Ac-pelgi or BAY3546828)
 is a new type of treatment under development for men with mCRPC who have already received
 available treatments or have few treatment options available. It works by binding to a
 protein on the surface of the cancer cells called prostate specific membrane antigen (PSMA).
 As it gives off a type of radioactivity that travels a very short distance, it kills the
 nearby (cancer) cells that express PSMA.
 
 The main purpose of this first-in-human study in men with mCRPC is to learn:
 
 - How safe different doses of 225Ac-pelgi are.
 
 - To what degree medical problems caused by 225Ac-pelgi can be tolerated by the
 participants?
 
 - Which dose of 225Ac-pelgi is optimal for treatment (safe and working well)?
 
 - How good is 225Ac-pelgi's anticancer activity?
 
 To answer this, the researchers will look at:
 
 - The number and severity of medical problems that the participants have after treatment
 with 225Ac-pelgi (per dose level).
 
 - The ratio of medical problems and anticancer activity per dose.
 
 - Anticancer activity of the optimal 225Ac-pelgi dose as proportion of participants who
 have at least halved prostate-specific antigen (PSA) levels after 12 weeks of treatment
 or later and/or shrunken or no longer detectable tumors.
 
 - The lowest PSA level reached after treatment start.
 
 Doctors keep track of all medical problems (also called adverse events) that participants
 have during the study, even if they do not think that they might be related to the study
 treatment.
 
 Anticancer activity is measured using cancer imaging techniques and change in blood level of
 a protein called PSA. PSA is made by normal and by cancerous cells in the body. The PSA level
 is taken as a marker for prostate cancer development and is usually elevated in men with
 mCRPC.
 
 In addition, researchers want to find out how 225Ac-pelgi moves into, through and out of the
 body.
 
 The study will have two parts. The first part, called dose escalation, is done to find the
 most appropriate dose and schedule that can be given in the second part of the study. For
 this, each participant will receive one of the predefined increasing doses of 225Ac-pelgi as
 an infusion into the vein. All participants in part 2, called dose expansion, will receive
 the most appropriate dose and schedule identified from the first part of the study. More than
 one dose level or schedule from part 1 may be tested. Both the participants and the study
 team know what treatment the participants will take.
 
 Participants in this study will take the study treatment 225Ac-pelgi once in a period of 6
 weeks called a cycle. Each participant will have 4 of these treatment cycles, if the
 participant benefits from the treatment.
 
 Each participant will be in the study for up to nearly six years, including a first test
 (screening) phase of a maximum of 28 days, up to 12 months of treatment depending on the
 participant's benefit, and a follow-up phase of 60 months after the end of treatment. The
 following visits to the study site are planned: 2 during the screening phase, 8 in the first
 treatment cycle, 7 in subsequent cycles, and a visit 6 to 12 weeks after the last dose. In
 the following 12 months, visits are planned every 6 weeks and during the next 48 months phone
 calls or clinic visits are planned approximately every 12 weeks.
 
 In addition, a sub study during the dose escalation part will gather information on the
 distribution of the study treatment in the body, the proportion that binds to the cancer
 cells, and the resulting radiation at the tumor site.
 
 During the study, the study team will:
 
 - Do physical examinations
 
 - Check vital signs such as blood pressure, heart rate, and body temperature
 
 - Take blood, and urine samples
 
 - Examine heart health using echocardiogram and electrocardiogram (ECG)
 
 - Take tumor samples
 
 - Track 225Ac-pelgi in the body using gamma imaging (only selected sites)
 
 - Check the tumor status using PET (positron emission tomography), CT (computed
 tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan
 
 - Ask questions about the impact of the disease on the participants' wellbeing and
 activities of daily life (Eastern Cooperative Oncology Group Performance status (ECOG
 PS)).

ICD-10 Classifications