Clinical Trials

Inclusion Criteria:

• Ability to understand and sign an approved informed consent form (ICF) and comply with all protocol requirements.
• Participants aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status:
  • Phase 2 ECOG PS 0 or 1
  • Phase 3 ECOG PS 0 to 2
• Diagnosis of adenocarcinoma of prostate proven by histopathology.
• Must have ≥ one unresectable metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to the first dose of study treatment.
• Must have had prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
• Progressive mCRPC. Documented progressive mCRPC will be based on at least one of the following criteria:
  • Serum/plasma PSA progression defined as two consecutive increases in PSA over a previous reference value measured at least one week prior. The minimal start value is 1.0 ng/mL.
  • Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for nonnodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions. 
  • Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (per PCWG3 criteria).
• Must have been previously treated with lutetium-PSMA therapy (lutetium-177 vipivotide tetraxetan or other lutetium-177-PSMA RLT). Treatment should be completed ≥ six weeks before the first dose of study treatment.
• Participants with known BRCA mutations should have received FDA-approved therapies such as PARP inhibitors, per Investigator discretion.
• Positive PSMA PET/CT scans, obtained with commercially available PSMA ligands (68GaPSMA-11 or 18F-DCFPyL), defined as at least one PSMA-positive metastatic lesion and no PSMA-negative lesions, per blinded independent central review.
• Participants must have adequate organ function:
  • Hemoglobin concentration ≥ 9.0 g/dLi
  • Platelet counts ≥ 100 × 109 /Li
  • ANC ≥ 1.5 × 109 /Li
    • Hematological criteria cannot be met with ongoing or recent blood transfusions (within 14 days prior to the first dose of study treatment) or require growth factor support (within 21 days prior to the first dose of study treatment).
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 × ULN.
    • Phase 3: ALT or AST ≤ 5.0 × ULN if liver metastases are present.
  • Total bilirubin ≤1.5 × the institutional ULN. For participants with known Gilbert’s Syndrome ≤ 3 × ULN is permitted.
  • Albumin > 3 g/dL.
  • Creatinine clearance ≥ 60 mL/min based on Cockcroft-Gault formula.
• For participants who have partners of childbearing potential: Partner and/or participant must not be planning to conceive and must use a method of birth control with adequate barrier protection deemed acceptable by the Principal Investigator during the study treatment and for six months after last study drug administration.

Exclusion Criteria:

• Previous treatment with any of the following within six months of the first dose of study treatment: samarium-153, rhenium-186, rhenium-188, RADIUM-223, hemi-body irradiation. Participants who received previous treatment with other RLTs not specified in eligibility criteria are excluded.
• Only for the Phase 2 segment, participants who progress within two cycles of prior treatment with lutetium-PSMA therapy (lutetium-177 vipivotide tetraxetan or other lutetium RLT) will be excluded.
• Participants who received more than two prior lines of cytotoxic chemotherapy for CRPC.
• All prior treatment-related adverse events must have resolved to Grade ≤1 (CTCAE v5.0). Alopecia and stable persistent Grade 2 peripheral neuropathy may be allowed at the discretion of the Investigator.
• Participants with known, unresolved urinary tract obstruction are excluded. If suspected, evidence of obstruction by 99mTc renal scan might be performed at the Investigator’s discretion.
• Administration of any systemic cytotoxic or investigational therapy ≤ 30 days of the first dose of study treatment or five half-lives, whichever is shorter. Completion of large-field external beam radiotherapy ≤four weeks of the first dose of study treatment.
• Transfusion-dependent participants. Hematological criteria cannot be met with ongoing or recent blood transfusions (within 14 days prior to the first dose of study treatment) or require growth factor support (within 21 days prior to the first dose of study treatment).
• Participants with a history of central nervous system (CNS) metastases are excluded, except those who have received therapy (surgery, radiotherapy, gamma knife) and are neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity for a minimum of 28 days. Participants with epidural disease, canal disease, and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For participants with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast).
• Symptomatic cord compression or clinical or radiologic findings indicative of impending cord compression.
• Participants with any liver metastases will be excluded from the Phase 2 segment of the study.
• Participants with skeletal metastases presenting as a superscan on a 99mTc bone scan or PSMA PET/CT.
• Previous or concurrent cancer that is distinct from the cancer under investigation in primary site or histology, except treated cutaneous basal cell carcinoma or squamous cell carcinoma and superficial bladder tumors. Any cancer curatively treated >two years prior to the first dose of treatment is permitted.
• Concurrent serious (as determined by the investigator) medical conditions, including but not limited to New York Heart Association class III or IV congestive heart failure, unstable ischemia, uncontrolled symptomatic arrhythmia, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant comorbid conditions, such as uncontrolled baseline pain and symptoms (nociceptive and neuropathic) or inadequate pain relief with doses of opioid analgesics that in the opinion of the Investigator would impair study participation or interfere with the objectives and assessments of the study.
• Major surgery ≤ 30 days prior to the first dose of study treatment

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/13/2024. Questions regarding updates should be directed to the study team contact.