Pacritinib in Participants With Metastatic Castrate-Resistant Prostate Cancer That Progressed on or After Prior Treatment With Androgen Receptor Signaling Inhibitors

Inclusion Criteria

• •I. To be eligible for screening:
• •1. Patients aged ≥ 18 years.
• •2. Histologically or cytologically confirmed prostate adenocarcinoma.
• •3. Have current evidence of metastatic disease documented by either bone scan, CT/MRI and/or PSMA PET scan
• •4. Have disease that progressed while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) and during or after treatment with at least one androgen receptor signaling inhibitor (ARSI) (e.g., abiraterone acetate, enzalutamide, apalutamide, darolutamide) for metastatic hormone-sensitive prostate cancer (HSPC) (mHSPC or nmHSPC) or mCRPC.
• •a. Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel. Disease progression could be prostate-specific antigen (PSA) based or radiographic progression per Prostate Cancer Working Group 3 (PCWG3) guidelines.
• •5. Screening serum testosterone \< 50 ng/dL.
• •6. Eastern Cooperative Oncology Group (ECOG), Performance Status grade 0-1 or Karnofsky Performance Status ≥ 70
• •7. No prior janus kinase2 (JAK2) inhibitor treatment.
• •8. Left ventricular cardiac ejection fraction of ≥ 50% by echocardiogram or multigated acquisition (MUGA) scan.
• •9. Adequate organ function as defined by the following laboratory values at screening:
• •1. Serum aspartate transaminase (AST), serum glutamic oxaloacetic transaminase (SGOT), serum alanine transaminase (ALT) and serum glutamic pyruvic transaminase (SGPT) \< 2.5 x upper limit of normal (ULN).
• •2. Total serum bilirubin ≤ 1.5 x ULN. In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 × ULN, the subject may be eligible).
• •3. Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed.
• •4. Estimated glomerular filtration rate (GFR) \> 45 ml/min using the Cockroft-Gault equation.
• •5. Platelets ≥ 100,000/mL independent of transfusion and/or growth factors within three months
• •6. Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within three months
• •7. Absolute neutrophil count ≥ 500/µL.
• •8. Serum albumin ≥ 3.0 g/dL.
• •9. Adequate coagulation defined by prothrombin time (PT)/international normalized ratio (INR) and PTT ≤ 1.5 ULN.
• •10. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
• •a. Practice effective barrier contraception and another effective method of birth control if he is having sex with a woman of childbearing potential during the entire study period and through 30 calendar days after the last dose of study agent
• •11. Ability to understand a written informed consent document, and the willingness to sign it.
• •II. To be eligible for treatment:
• •1. Patients must meet all screening criteria described above.
• •2. Patients must provide tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed. Participants with bone-only or bone-predominant disease may provide a bone biopsy sample. A tumor sample must be obtained within 30 days of treatment.
• •3. STAT5 activation levels need to be high, with positive STATA5 activation status defined as detectable nuclear localized Stat5 in \>5% of cancer cells from tissue obtained within 30 days of treatment.