Inclusion Criteria:
* Age \>18 years
* Documented histological or cytological diagnosis of PC
* Evidence of metastatic PC on imaging (bone scan and/or CT/MRI scan)
* Diagnosis of progressive metastatic, castration resistant prostate cancer
* Potential participant must be planning to receive Enzalutamide as their first line of therapy for castration resistant prostate cancer or have previously received up to one line of Abiraterone or an androgen receptor antagonist
* Willing to undergo a tumor biopsy prior to beginning therapy, if recent tissue samples are not available
* Willing to undergo a tumor biopsy of at least one metastatic site or primary prostate after \~4-6 weeks of therapy with both agents
* Participants without prior orchiectomy must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) therapy until permanent discontinuation of study treatment
* ECOG performance status of 0-1
* Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless specified below AE(s) are clinically nonsignificant and/or stable on supportive therapy
* Adequate organ and marrow function, based upon laboratory criteria within 14 days before first dose of study treatment
* Sexually active, fertile participants and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom with spermicide during the course of the study and for 4 months after the last dose of study treatment
* Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
Exclusion Criteria:
* Receipt of any type of biologic, or other systemic anticancer therapy (including investigational) except agents within 4 weeks before first dose of study treatment. Anti-resorptive bone agents are also allowed.
* Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.
* Prior exposure to taxane chemotherapy
* History of pneumonitis
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Participants must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible participants must be neurologically asymptomatic and without corticosteroid treatment for neurological indications at the time of first dose of study treatment.
* Participants with clinically significant dry eye or corneal abnormalities
* Currently taking certain anticoagulation medications, such as coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)
* Participant has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 X the laboratory ULN within 30 days before the first dose of study treatment.
* Participants should not receive strong CYP2C8 or strong P-gp inhibitors; strong CYP3A4 or CYP2C8 inducers; and strong CYP3A4, CYP2C9 and CYP2C19 substrates while participating in the trial, unless utilized with caution to treat a drug-related AE when no alternative is available and discussed with the Medical Monitor.
* Participant has uncontrolled, significant intercurrent or recent Cardiovascular disorders including, but not limited to, the following conditions:
i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \>140 mm Hg systolic or \>90 mm Hg diastolic despite optimal antihypertensive treatment.
iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
* Corrected QT interval calculated by the Fridericia formula (QTcF) \> 470 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
* Inability to swallow tablets.
* Use of herbal products that may decrease PSA levels within 4 weeks prior to enrollment
* Previously identified allergy or hypersensitivity to components of the study treatment formulations.
* Diagnosis of another type of cancer within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy.
* Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
