Novel ACK1 Inhibitor (R)-9b in Patients With Prostate Cancer

Inclusion Criteria: 1. Histologically or cytologically confirmed prostate cancer (mCRPC). 2. Must have evidence of metastatic disease on conventional imaging (eg. CT, MRI, technetium bone scan). May have any type or location of metastases (bone, lymph node, visceral). RECIST 1.1 measurable disease is not required; may have bone-only metastases. 3. Ongoing androgen deprivation therapy (ADT) at time of study enrollment (GnRHR agonist such as leuprolide, goserelin, triptorelin, buserelin, histrelin; GnRHR antagonists such as degarelix or relugolix), or history of surgical castration. 4. Must have evidence of castrate testosterone levels with baseline serum testosterone level of 50 ng/dL or less at time of study start, and castrate levels should be maintained throughout study. 5. Evidence of progressive castration-resistant prostate cancer, defined as at least 2 consecutive rises of PSA, at least 1 week apart with the last PSA ≥ 2 ng/mL or by evidence of radiographic progression. 6. Patients must have had prior disease progression on at least one novel hormonal agent (NHA) (eg enzalutamide, abiraterone, apalutamide, darolutamide, etc.); treatment with NHA could have occurred in the castration-sensitive or castration-resistant setting. 7. Prior palliative radiation therapy for bone metastasis (must be complete ≥ 14 days prior to enrollment) or any other radiation therapy (must be complete ≥ 28 days prior to enrollment) is allowed. Prior definitive radiation therapy for localized prostate cancer is allowed. 8. Recovery to baseline or ≤ grade 1 from toxicities related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy. 9. At least 18 years of age. 10. ECOG performance status ≤ 1 11. Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,500/mm3 without granulocyte colony-stimulating factor support * White blood cell count ≥ 2,000/mm3 * Platelets ≥ 100,000/mm3 without transfusion * Hemoglobin ≥ 9.0 g/DL * Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3.0 x IULN) * AST(SGOT), ALT(SGPT) ≤ 3.0 x IULN * Serum creatinine ≤ 1.5 x IULN or calculated creatinine clearance ≥ 45 mL/min by Cockcroft-Gault * Serum albumin ≥ 2.8 g/dL * Urine protein/creatinine ration (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) (only evaluated if creatinine abnormal per criteria above * PT/INR or PTT \< 1.5 x IULN (PT/INR must be drawn \< 7 days prior to biopsy for those patients treated in MTD cohort), unless participant is receiving anticoagulant therapy and these are within intended therapeutic ranges for anticoagulant. 12. Corrected QT interval calculated by the Fridericia formula (QTcF) ≤ 500 ms (by ECG). 13. Ability to understand and willingness to sign an IRB approved written informed consent document (or that of the legally authorized representative, if applicable). 14. Willingness and ability to undergo biopsy for research component of the trial (for patients treated in MTD cohort) 15. Heterosexually active male patients (along with their female partners) are required to use two forms of acceptable contraception, including one barrier method, during participation in the study and for 5 months following the last day of study treatment. If a female partner of a male patient becomes pregnant during therapy or within 5 months after the last day of study treatment, the investigator must be notified in order to facilitate outcome follow-up. Exclusion Criteria: 1. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before first dose of study treatment. 2. Exclusively small cell variant of prostate cancer, or other prostate cancer histology that does not contain adenocarcinoma 3. Inability to swallow pills. 4. Presence of a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 calendar days of start of study treatment. Inhaled or topical steroids and adrenal replacement steroid doses \< 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. 5. Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, or superficial bladder cancer. Any history of prior malignancy must be reviewed by the PI. 6. Currently receiving any other investigational agents. 7. Any anti-androgen receptor agents or abiraterone (or similar CYP17,20 lyase inhibitor) within 14 days or 5 half-lives, whichever is longer, prior to the start of study drug. 8. Use of Radium-223 or other radioligand/radiopharmaceutical within 28 days prior to the start of study drug 9. Any gastrointestinal issues affecting absorption (e.g. gastrectomy, bowel resection, etc), as determined by the PI. 10. Blood transfusion within 28 days of screening. 11. Use of hormonal agents or supplements with potential anti-tumor activity against prostate cancer, as determined by the PI, within 28 days prior to the start of study drug. 12. Bone-modifying agents (eg zolendronic acid, denosumab, etc) may not be initiated after start of study drug; previously initiated agents may be continued while on trial. 13. Patients with 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). Eligible subjects must be neurologically asymptomatic. 14. History of seizures or seizure disorder. 15. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to (R)-9bMS used in the study. 16. Uncontrolled, significant intercurrent illness including, but not limited to, the following conditions: * Cardiovascular disorders: * Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias. * Uncontrolled hypertension defined as sustained blood pressure (BP) \> 160 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment. * Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within six months before the first dose of study treatment. * Subjects with a diagnosis of incidental, subsegmental PE or DVT within six months are allowed if stable, asymptomatic, and treated with anticoagulation for at least 1 week before the first dose of study treatment. * Gastrointestinal (GI) disorders associated with a high risk of perforation or fistula formation, as determined by the PI: * The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction. * Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within six months before the first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before the first dose. * Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before the first dose. * Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation. * Lesions invading or encasing any major blood vessels. * Other clinically significant disorders that would preclude safe study participation. * Serious non-healing wound/ulcer/bone fracture. * Uncompensated/symptomatic hypothyroidism. * Moderate to severe hepatic impairment (Child-Pugh B or C). 17. Active hepatitis B or C or active HIV per review of medical records. Patients with well-controlled HIV or hepatitis B or C, or who have had curative treatment for hepatitis C, may be considered if they meet all other criteria and after discussion with the PI using the following criteria for guidance: https://www.fda.gov/media/121319/download 18. History of organ allograft. 19. Major surgery (e.g., GI surgery removal or biopsy of brain metastasis) within eight weeks before the first dose of study treatment. Complete wound healing from major surgery must have occurred one month before the first dose and from minor surgery (e.g., simple excision, tooth extraction) at least ten days before the first dose (with the exception of the baseline biopsy, which must have occurred no less than 6 days prior to the first dose). Patients with clinically relevant ongoing complications from prior surgery are not eligible. 20. Any other medical intervention or condition, which, in the opinion of the PI or treating physician, could compromise patient safety or adherence with the study requirements (including biopsies), or confound results of the study, over the treatment period. 21. Any known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 22. Patients cannot have concurrent enrollment on other phase I, II, or III investigational treatment studies in which they are actively receiving treatment (participation in long-term follow-up is acceptable).