GZ17-6.02 in Advanced CRPC After Progression on Anti-Androgen Therapy

This single-arm phase Ib study will assess whether GZ17-6.02, a combination of curcumin, harmine, and isovanillin, delays radiographic progression of castration-resistant prostate cancer among men previously treated with androgen deprivation therapy and an androgen receptor pathway inhibitor. All participants in the study will receive GZ17-6.02. The study will also assess the safety and tolerability of GZ17-6.02 and explore patient-reported outcomes.

Inclusion criteria

• Patients diagnosed with prostate cancer and treated with androgen deprivation therapy (ADT) and at least one androgen receptor pathway inhibitor (ARPI) (eg, abiraterone, enzalutamide, apalutamide or darolutamide). Previous prostate-specific membrane antigen (PSMA)-targeted therapy or cytotoxic chemotherapy is allowed but not required.
• Androgen levels ≤50 ng/dL (≤1.73 nmol/L).
• Disease progression following ADT and ARPI treatment described
• PSA progression over 2 assessments, defined as rising PSA values from 2 consecutive assessments with an interval of at least 7 days between assessments. PSA levels prior to study enrollment are considered and appropriate for inclusion.
• Measurable disease by RECIST v1.1 on chest/abdomen/pelvis CT or evaluable disease observed on bone scan.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Appropriate hepatic function defined by a total bilirubin (TBL) ≤1.5 × the upper limit of normal (ULN), alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) ≤3 × ULN at screening.
• Appropriate kidney function defined by calculated or actual creatinine clearance ≥30 mL/min
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3.
• Platelets ≥100,000 cells/mm3.
• Serum hemoglobin level ≥8 g/dL.
• Agree to not donate blood or sperm during the study and for 90 days after the last dose of study treatment.
• Patients with sexual partners of childbearing potential must agree to use highly effective methods of contraception throughout the study
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Any investigational agent:

within 4 weeks OR within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, before initiating study treatment.

• Low PSA (≤10 ng/mL) at initial presentation (before ADT or at symptomatic progression in the castrate setting) plus high volume (≥20) bone metastases.
• Simultaneous enrollment in any other cancer treatment interventional clinical trial.
• Active, uncontrolled diarrhea leading to dehydration or electrolyte disturbances not controlled with oral repletion.
• Grade ≥3 uncontrolled infection.
• Major surgery (in the opinion of the treating investigator) ≤3 weeks before initiating study treatment.
• Not having fully recovered to a grade of 1 or lower from any surgery-related adverse effects within the 3 weeks preceding the start of the study treatment.
• Small cell, anaplastic, or neuroendocrine component.
• Known active brain metastasis.
• Known active leptomeningeal disease.
• Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the medications included in the study treatment must be discontinued ≥2 weeks prior to initiating study treatment unless otherwise noted:

• Monoamine oxidase inhibitors (MAOI) use; must discontinue use 10 days prior to initiating study therapy.
• Strong or moderate CYP1A2, CYP3A4 and CYP2C19 inhibitors.
• Rucaparib, Olaparib and Talazoparib, due to their common findings of liver enzyme elevation.
• Inability to swallow medication.
• Known hypersensitivity to GZ17-6.02 components (curcumin, harmine, and isovanillin) or excipients.
• Known or suspected malabsorption condition or obstruction.
• Active untreated hepatitis B or C" and "Known liver cirrhosis of any cause, active nonalcoholic steatohepatitis, or nonalcoholic fatty liver disease. Note: no additional testing necessary to confirm
• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements