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About
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:
To answer this, the researchers will look at:
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 30 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:
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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 androgen deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
Prior taxane treatment:
Prior treatment with an established 177Lu-PSMA therapy (i.e., dose activity and cycles comparable to approved treatments) is required for participants in Dose Expansion Group C only. More specifically, to qualify for this expansion group, participants must meet all of the following criteria:
Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements within 30 days before start of study intervention:
Participants must have at least one Prostate-specific membrane antigen (PSMA)-positive distant metastatic lesion on the screening PSMA PET/CT scan using the study-designated PSMA PET tracers, as determined by the site Investigator. For eligibility purposes, a PSMA-positive lesion must have activity greater than the liver by visual assessment of the screening PSMA PET/CT. A PSMA-positive metastatic lesion should not correspond to a normal tissue structure or benign lesion.
Documented progressive mCRPC per PCWG3, defined as meeting at least one of the following criteria:
Exclusion criteria
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.
Prior systemic anticancer therapy including chemotherapy, NAAD, biologic therapy, immunotherapy, or investigational therapies within 4 weeks of the start of study intervention, except luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH). Start of study intervention is allowed in shorter timeframes if 5 half-lives of the prior drug(s) have elapsed.
Prior radiopharmaceutical treatment using actinium-225.
Other prior radiopharmaceutical treatments:
Note: Participants who have discontinued 177Lu-PSMA treatment due to intolerance or loss of initial response are excluded from Group C.
Dose Expansion Group C: Presence of any liver metastasis (Bakht et al. 2023).
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232 participants in 4 patient groups
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Bayer Clinical Trials Contact
Data sourced from clinicaltrials.gov
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