BAY3546828 for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+27 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Bayer
Must be taking: Novel androgen axis drugs
Must not be taking: Actinium-225, Radiopharmaceuticals
Disqualifiers: Psma-negative lesions, Recent anticancer therapy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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 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:
* 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 (generally available at all study sites)
* Check the tumor status using PET (positron emission tomography), CT (computed tomography) or MRI (magnetic resonance imaging) and 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)).
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain anticancer therapies within 4 weeks before starting the study treatment, except for specific hormone therapies. It's best to discuss your current medications with the study team.
Eligibility Criteria
This trial is for men with advanced metastatic castration-resistant prostate cancer (mCRPC) who have tried other treatments or have limited options. They must have a specific type of prostate cancer, confirmed by tests, and treated previously with certain drugs like enzalutamide or abiraterone. Participants need to maintain low testosterone levels through treatment or surgery and should be physically able to perform daily activities with minimal assistance.Inclusion Criteria
My scans show at least one PSMA-positive spot away from my prostate.
I have previously received 177Lu-PSMA therapy.
I have specific requirements for prior taxane treatment based on my treatment group.
+6 more
Exclusion Criteria
I have received radiopharmaceutical treatments based on my treatment group.
I finished my last cancer treatment less than 6 weeks ago.
I haven't had cancer treatment in the last 4 weeks.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
2 visits (in-person)
Treatment
Participants receive 225Ac-pelgi in cycles, with dose escalation and expansion phases to determine optimal dosing
12 months
8 visits in the first cycle, 7 visits in subsequent cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
60 months
Visits every 6 weeks for 12 months, then every 12 weeks
Participant Groups
The study is testing the safety and effectiveness of a new treatment called Actinium-225-macropa-pelgifatamab (BAY3546828). It targets a protein on cancer cells to deliver radiation directly to them. The trial has two parts: finding the best dose and then giving that dose over four cycles every six weeks if beneficial. Researchers will monitor participants' health, take samples, use imaging techniques, and ask about their wellbeing.
4Treatment groups
Experimental Treatment
Group I: Dose expansion group C of BAY3546828Experimental Treatment1 Intervention
Participants with advanced mCRPC after prior Lutetium-177 labeled PSMA ligand (177Lu-PSMA) treatment.
Group II: Dose expansion group B of BAY3546828Experimental Treatment1 Intervention
Participants with advanced mCRPC who have not received taxane chemotherapy since becoming castration-resistant. No prior radionuclide therapy.
Group III: Dose expansion group A of BAY3546828Experimental Treatment1 Intervention
Participants with advanced mCRPC with at least 1 but no more than 2 prior taxane regimens. No prior radionuclide therapy
Group IV: Dose escalation of BAY3546828Experimental Treatment1 Intervention
Participants with advanced metastatic castration-resistant prostate cancer (mCRPC) will receive 225Ac-pelgi dose in a stepwise fashion, according to a predefined dose escalation scheme.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
BC Cancer - Vancouver SiteVancouver, Canada
Princess Margaret Cancer Centre - University Health Network - Department of Medical Oncology and HematologyToronto, Canada
Juravinski Cancer Centre - Clinical Trials DepartmentHamilton, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM) - HopiMontreal, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
BayerLead Sponsor
References
The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer. [2021]The prostate-specific membrane antigen (PSMA) has received increased consideration during the past few years as an excellent target for both imaging and therapy of prostate cancer. After many years of outstanding preclinical research, the first significant step forward in clinical use was achieved in 2008 with the first human experience with the small-molecule PSMA inhibitors 123I-MIP-1972 and 123I-MIP-1095. A clinical breakthrough followed in 2011 with 68Ga-PSMA-11 for PET imaging and 131I-MIP-1095 for endoradiotherapy of metastatic prostate cancer. Since then, PET/CT with 68Ga-PSMA-11 has rapidly spread worldwide, and endoradiotherapy with PSMA ligands has been conducted at increasing numbers of centers. 68Ga-PSMA-11 is currently the subject of multicenter studies in different countries. Since 2013, 131I-related PSMA therapy has been replaced by 177Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter studies. Alternative PSMA ligands for both imaging and therapy are available. Among them is 99mTc-MIP-1404, which has recently entered a phase 3 clinical trial. This article focuses on the highlights of the development and clinical application of PSMA ligands.
68Ga-PSMA PET/CT Replacing Bone Scan in the Initial Staging of Skeletal Metastasis in Prostate Cancer: A Fait Accompli? [2021]Label="PURPOSE"> 68Ga ligands targeting prostate-specific membrane antigen (PSMA) are rapidly emerging as a significant step forward in the management of prostate cancer. PSMA is a type II transmembrane protein with high expression in prostate carcinoma cells. We prospectively evaluated the use of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer and compared the results to those for technetium-99m (99mTc)-10-metacyloyloxydecyl dihydrogen phosphate (MDP) bone scintigraphy (BS).
Preclinical Evaluation of a Fibroblast Activation Protein and a Prostate-Specific Membrane Antigen Dual-Targeted Probe for Noninvasive Prostate Cancer Imaging. [2023]Prostate-specific membrane antigen (PSMA) is a prostate cancer target that plays a crucial role in prostate cancer diagnosis and therapy. Herein, a novel dual-targeted imaging probe, [68Ga]Ga-FAPI-PSMA, was prepared by radiolabeling conjugated DOTA-FAPI-PSMA with the short half-life radionuclide gallium-68 (68Ga), which is dedicated to prostate cancer diagnostic imaging. In vitro, [68Ga]Ga-FAPI-PSMA had higher affinity for the PSMA and FAP high-expressing cell lines 22Rv1 and U87 MG with IC50 values of 4.73 and 2.10 nM, respectively, than in the corresponding negative expression cell lines PC3 and A549, and significant differences in cell uptake were also observed. In vivo, [68Ga]Ga-FAPI-PSMA was rapidly cleared from the body, and the estimated radiation dose was relatively low compared with several other FAPI probes. In 22Rv1 and U87 MG tumor xenografts, [68Ga]Ga-FAPI-PSMA rapidly accumulated in tumors after administration, and the best images can be obtained at 1 h postinjection. In conclusion, the dual-targeted probe [68Ga]Ga-FAPI-PSMA was successfully prepared for in vivo prostate cancer PET/CT imaging.
Efficacy and Safety of Actinium-225 Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Prostate Cancer: A Systematic Review and Metanalysis. [2023]Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an alpha emitter, is expected to have higher efficacy and fewer side effects compared to the beta-emitters such as Lutetium-177. We have performed a meta-analysis to assess the therapeutic responses, survival effects, and significant side effects of Ac-225 PSMA RLT in patients with mCRPC.
68Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis. [2022]Label="CONTEXT"> 68Gallium prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC-PSMA (68Ga-PSMA) is a promising radiotracer for positron emission tomography (PET)/computed tomography (CT) of prostate cancer.