• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration

• Males age ≥ 18 years with progressive metastatic, castration-resistant prostate cancer, previous adenocarcinoma histology confirmation required

• Ability to understand a written informed consent document, as determined by the study physician or designee

• Surgical castration or continuous medical castration ≥ 8 weeks prior to screening; serum testosterone \< 50 ng/dL

• Have progressed on prior abiraterone treatment by Prostate Cancer Working Group 3 prostate specific antigen (PSA) criteria

‣ PSA must rise on two measurements at least 1 week apart in order to be eligible. Refer to PCWG3 for clarification.

⁃ Most Recent absolute PSA must be \> 2.0 ng/mL

• Patient meets definition of poor responder to abiraterone by one of the following:

‣ Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting (abiraterone started within 4 months of starting continuous androgen deprivation therapy \[ADT\]): \< 12 months duration on abiraterone

⁃ Abiraterone started in castration-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone due to progression or failure to achieve PSA50 response while on therapy

• The patient's current or most recent treatment is ADT and abiraterone. Participants must sign consent within 30 days of discontinuing abiraterone or prior to stopping abiraterone

• Patients must be willing to undergo metastatic tumor biopsy during screening. If no metastatic lesion is safely accessible to tumor biopsy, this requirement will not be required

• 50% of patients must have measurable disease by RECIST 1.1 criteria

‣ Once 50% of total expected cohort has non-measurable disease, only patients with measurable disease by RECIST 1.1 criteria will be eligible. (Percentages with measurable disease are not relevant within dose escalation. Once dose expansion is started, those at expansion dose would be included in percentage evaluation.)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 (grade 2 ECOGs should be related to disease and thus potentially reversible)

• A male participant must agree to use of contraception during the treatment period and for at least 90 days after the last dose of study drug. Female partners of male patients should also use contraception for 90 days after the last dose of study drug if they are of childbearing potential

• Platelets ≥ 125,000/mm\^3 (obtained within 28 days prior to starting study therapy) (if creatinine clearance \[CrCl\] is between 30-59, the platelet entry criteria is \> 150,000/mm\^3)

• Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained within 28 days prior to starting study therapy)

• Hemoglobin ≥ 11 g/dL (obtained within 28 days prior to starting study therapy) No transfusions within 90 days prior to screening unless performed for acute bleeding

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (obtained within 28 days prior to starting study therapy) For patients with known liver metastasis: (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN

• Bilirubin ≤ 1.5 the upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 x ULN. For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL (obtained within 28 days prior to starting study therapy)

• Creatinine clearance (CrCl) ≥ 30 mL/min (obtained within 28 days prior to starting study therapy) For creatinine clearance estimation, the Cockcroft and Gault equation should be used