Patients must have an ECOG performance status of 0 to 2.
Patients must have had histological, pathological, and/or cytological confirmation of prostate cancer.
Patients must have a positive 68Ga-PSMA-11 PET/CT scan.
Patients must have extensive bone metastases (i.e., > 20 sites) on baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to beginning study therapy. If a patient also has soft tissue or visceral disease, it must be PSMA-positive on 68Ga-PSMA-11 PET/CT scan.
Group A Subjects: Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy, a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L) and must have received prior cytotoxic chemotherapy and/or a novel androgen axis drug (e.g., abiraterone or enzalutamide).
Group B Subjects: Patients must have ongoing androgen deprivation therapy (ADT) and either prior orchiectomy or be medically castrate using LHRH agonists/antagonists in order to achieve adequate suppression of serum testosterone (<50 ng/dL) but must not have received prior cytotoxic chemotherapy or novel androgen axis drugs (e.g., abiraterone or enzalutamide). (S. Africa only)
Patients must have recovered or stabilized to ≤ Grade 2 or baseline from all clinically significant toxicities related to prior prostate cancer therapy.
Determination of disease progression on treatment prior to enrollment. Progressive disease for study entry.
Patients must have adequate organ function.
Patients must be stable on a bisphosphonate or denosumab regimen for ≥15 days prior to anticipated C1D1 date of receiving 225Ac-PSMA-617 are eligible.
Known HIV-positive patients who are healthy and have a low risk of AIDS-related outcomes are eligible. HIV testing is required.
For patients who have partners of childbearing potential.
Other protocol-defined inclusion criteria may apply.
Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation or previous PSMA-targeted radioligand therapy.
Any investigational agents within 28 days of the anticipated C1D1 of 225Ac-PSMA-617 therapy.
Known hypersensitivity to the components of the study therapy or its analogues.
Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
Transfusion for the sole purpose of eligibility into the study.
Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired.
Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with a prior history of malignancy who have been disease free for more than 3 years are eligible.
Other protocol-defined exclusion criteria may apply.