Inclusion Criteria:

• Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
  • NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Histologically confirmed prostate cancer.
• High volume metastatic disease defined as visceral metastases and/or ≥ 4 bone metastases on standard CT or bone scan imaging. Patients with high volume disease on novel imaging scans including Axumin PET or PSMA PET are only eligible if they meet criteria on standard CT and bone scan.
• ADT for ≤ 3 months by Day 1 of study chemotherapy; Prior episodes of ADT are allowed (i.e., ADT used previously in courses of radiation).
  • NOTE: Standard of care ADT continues for the duration of this study.
• Testosterone 1 month prior to study treatment start. Patients must continue primary ADT with an LHRH analogue if they have not undergone orchiectomy. Patients who have not yet started ADT at the time of enrollment may initiate ADT via LHRH agonist or antagonist therapy during the screening period and will not be required to document a castrate level of testosterone prior to initiating chemotherapy.
• ECOG Performance Status 0 or 1.
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
  • Absolute neutrophil count ≥ 1.5 × 10^9 /L;
  • Platelets ≥ 100 × 10^9 /L;
  • Hemoglobin ≥ 9 g/dl;
  • Serum creatinine ≤ 1.5mg/dL or estimated creatinine clearance ≥ 50 ml/min;
  • In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN. If the patient has liver metastases, ALT and AST < 5 x ULN; 
  • Total bilirubin < ULN; or total bilirubin ≤ 3 .0 x ULN or direct bilirubin ≤ 1.5 x ULN in patients with well-documented Gilbert’s Syndrome.
• Sexually active persons must use a condom during intercourse while taking study drugs and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized persons in order to prevent delivery of the drug via seminal fluid. Fertile participants must use a condom with spermicide (double barrier method).
• Age ≥ 18 years.

Exclusion Criteria:

• Prior exposure to any chemotherapy, PARPi, or immunotherapy for prostate cancer.
• Pure Small Cell Carcinoma.
• Prior abiraterone, apalutamide, darolutamide, or enzalutamide, unless therapy was for < 4 weeks.
• Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14 days or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days of the date of the first dose.
• Other systemic therapies for prostate cancer within 28 days or 5 half-lives, whichever is shorter, prior to day 1 of chemotherapy (with the exception of anti-androgens like bicalutamide).
• PSA < 2.0 ng/mL at diagnosis.
• If present, peripheral neuropathy must be ≤ Grade 1.
• Patients with an active second malignancy that could, in the investigator’s opinion, potentially interfere with the patient’s ability to participate and/or complete this trial.
• Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
  • At least 4 weeks from prior therapy completion (including radiation and/or surgery) prior to starting the study treatment;
  • Clinically stable CNS tumor at the time of screening;
  • Baseline screening for CNS metastases is not required unless presence of signs and/or symptoms of involvement.
• Known history of severe hypersensitivity to drugs formulated with polysorbate 80.
• Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of treating investigator.
• Patient has a history of non-compliance to medical regimen or inability to grant consent.