NCT04946370 · Weill Medical College of Cornell University
Phase I/II Trial of Pembrolizumab and Androgen-receptor Inhibitor With or Without 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer
What this study is about
This is a phase I/II study investigating the combination of 225Ac-J591 (a drug that can deliver radiation to prostate cancer cells) with pembrolizumab (immunotherapy, a drug that increases the immune system's ability to destroy cancer cells).
View original scientific description
This is a phase I/II study investigating the combination of 225Ac-J591 (a drug that can deliver radiation to prostate cancer cells) with pembrolizumab (immunotherapy, a drug that increases the immune system's ability to destroy cancer cells). This study will assess whether 225Ac-J591 + pembrolizumab + androgen receptor inhibitor (ARI) is more effective against prostate cancer than pembrolizumab + ARI alone.
Interventions
DRUG
225Ac-J591
Alpha-emitter Actinium-225 conjugated to the anti-PSMA antibody J591.
DRUG
Pembrolizumab
Pembrolizumab will be administered intravenously, 400mg every 6 weeks. Patients may receive maximum 18 cycles of therapy, approximately 2 years.
DRUG
Androgen receptor inhibitor
Patients will receive an oral androgen receptor inhibitor (ARI). Examples include enzalutamide, apalutamide, darolutamide. Dosing will be the standard dosing, as described by the package insert.
DIAGNOSTIC_TEST
68Ga-PSMA-11
\[185 ±74 MBq or 5 ±2 mCi\] intravenous during screening and 12 weeks. Imaging agent for PSMA PET/CT.
Primary outcome measures
Proportion of patients with dose-limiting toxicity (DLT) following treatment with pembrolizumab and 225Ac-J591
Time frame: From visit 1 through 12 weeks on study
Primary outcome for phase I; DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. There will be 12 weeks of safety follow-up following visit 1.
Determination of optimal dose of 225Ac-J591 for phase II
Time frame: From visit 1 through 12 weeks on study
Primary outcome for phase I; following 12 weeks of safety follow-up, the study team will make a determination of the 225Ac-J591 dose for phase II (either 65 or 90 KBq/kg).
Change in composite response rate of pembrolizumab and ARPI with or without 225Ac-J591
Time frame: Will be collected at the time of visit 1 and up to 100 months
The primary outcome for phase II will be response, a composite of: PSA decline greater than 50% of baseline, measurable disease response by imaging criteria, conversion of circulating tumor cell count to favorable or undetectable.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Male participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of prostate adenocarcinoma.
- A male participant must agree to use a contraception during the treatment period and for at least 4 months after the last dose of study treatment and refrain from donating sperm during this period.
- Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: PSA progression, Objective radiographic progression in soft tissue, New bone lesions
- Evaluable for response with at least one of the following:
- Measurable disease by RECIST 1.1
- Detectable (\>0) CTC by CellSearch
- PSA of at least 5ng/dL
- ECOG performance status of 0-1
- Have serum testosterone ≤ 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy.
Where
- Boston, Massachusetts
- Brooklyn, New York
- New York, New York
Collaborators
United States Department of Defense, Merck Sharp & Dohme LLC
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 21, 2026 · Source of record for eligibility and locations