Efficacy Evaluation of VERU-111 for mCRPC in Patients Who Have Failed at Least One Androgen Receptor Targeting Agent

Inclusion Criteria:

• Provide informed consent.
• Be able to communicate effectively with the study personnel.
• Aged ≥18 years.
• Histological or cytologic proof of adenocarcinoma of the prostate not including thediagnosis of small cell carcinoma of the prostate of neuroendocrine pathology.
• Radiographic evidence of metastatic disease at baseline by CT scan, or MRI and bonescan, with confirmation of measurable disease by RECIST 1.1 and/or identifiablediscrete bone metastases by PCWG3.
• Known castration resistant prostate cancer, defined according to PCWG3 criteria.
• Have received at least one androgen receptor targeting agent (e.g. abiraterone,enzalutamide, darolutamide, or apalutamide).
• Subjects who have metastatic castration resistant prostate cancer that have maintainedor have previously been treated with ADT (while on-study, patients must receivecontinuous ADT. Either chemical or surgical castration by bilateral orchiectomy isacceptable) and have failed prior treatment with at least one androgen receptortargeting agent (e.g. abiraterone, enzalutamide, darolutamide, or apalutamide) definedas:
• Serum PSA progression of two consecutive increases in PSA over a previous referencevalue within 6 months of first study treatment, each measurement at least 2 weeksapart. Or
• Documented bone lesions by the appearance of two or more new lesions on bonescintigraphy or bi-dimensionally-measurable soft tissue metastatic lesion assessed byCT or MRI.
• Treatment with an alternative androgen receptor targeting agent is a reasonable nextline of therapy.
• Absolute PSA ≥2.0 ng/ml at screening.
• ECOG performance status <2.
• Participants must have normal organ and bone marrow function measured within 30 daysprior to administration of study treatment as defined below:
• Hemoglobin ≥9.0 g/dL with no blood transfusion in the past 30 days
• Creatinine clearance ≥60 mL/min (using Cockcroft-Gault equation)
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelet count ≥100 x 109/L
• Total bilirubin ≤ upper limit of normal (ULN) (or <2.5 x ULN for patients with knownGilberts disease)
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT))/Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤2.5 x ULN. NOTE: Patients with elevations in bilirubin, AST, or ALT should bethoroughly evaluated for the etiology of this abnormality prior to entry and patientswith evidence of viral infection should be excluded. Patients with chronic renal stentand stable creatinine elevation can be included in the study with writtendocumentation from the PI.
• Participants must have a life expectancy >3 months.
• Subjects must agree to use acceptable methods of contraception:
• If the study subject's partner could become pregnant, use acceptable methods ofcontraception from the time of the first administration of study medication until 6months following administration of the last dose of study medication. Acceptablemethods of contraception are as follows: Condom with spermicidalfoam/gel/film/cream/suppository [i.e.,barrier method of contraception], surgicalsterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partneruses oral contraceptives (combination estrogen/progesterone pills), injectableprogesterone or subdermal implants and a barrier method (condom used with spermicidalfoam/gel/film/cream/suppository).
• If female partner of a study subject has undergone documented tubal ligation (femalesterilization), a barrier method (condom used with spermicidalfoam/gel/film/cream/suppository)should also be used.-If female partner of a studysubject has undergone documented placement of an intrauterine device (IUD) orintrauterine system (IUS),a barrier method (condom with spermicidalfoam/gel/film/cream/suppository)should also be used.
• Other than metastatic prostate cancer, no evidence (within 5 years) of priormalignancies (except successfully treated basal cell or squamous cell carcinoma of theskin or other cancers treated with curative intent >3 years prior).
• Participants must agree to refrain from prolonged exposure to the sun or agree to useat least SPF 50 on all exposed skin and protective clothing during prolonged sunexposure throughout participation in this study and/or treatment with VERU- 111.
• Subject is willing to comply with the requirements of the protocol through the end ofthe study.

Exclusion Criteria:

• Known hypersensitivity or allergy to colchicine.
• Histologic identification of small cell carcinoma of the prostate or neuroendocrinepathology in either biopsy or prostatectomy tissue.
• A bone scan with evidence of superscan or superscan phenomenon, defined as:
• Uptake throughout the axial skeleton and proximal appendicular skeleton, oftensomewhat heterogeneous, or,
• Symmetrically intense and diffuse radiotracer uptake in the skeleton with absent ordiminished visualization of the genitourinary system and soft tissues, or,
• Defined in the bone scan report as a superscan or superscan phenomenon. NOTE: MedicalMonitor should be consulted prior to screening of a patient if a superscan orsuperscan phenomenon is suspected or possible, but undetermined by any of the abovedefinitions.
• Has received external-beam radiotherapy within the last 2 weeks prior to start ofstudy treatment.
• Patients with a QT interval corrected by Fridericia's formula of >480 ms.
• Patients receiving full dose warfarin therapy are not eligible for study.
• Patients with prior history of a thromboembolic event within the last 6 months.
• Participation in another clinical study with an investigational product during thelast 6 months prior to randomization into this study.
• Patients should be excluded if they have had prior systemic treatment with priortaxane chemotherapies (for greater than 2 cycles) for advanced prostate cancer.Patient can have up to 2 cycles of prior taxane chemotherapy greater than one yearprior to randomization and remain eligible for inclusion in this study. Taxaneexposure in the adjuvant or neoadjuvant setting is allowed (maximum of 6 cycles).
• Any treatment modalities involving major surgery within 4weeks prior to the start ofstudy treatment.
• Patients are excluded if they have known brain metastases or leptomeningealmetastases.
• Patients should be excluded if they have a positive test for hepatitis B virus surfaceantigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicatingacute or chronic infection.
• Has imminent or established spinal cord compression based on clinical findings and/orMRI.
• Any other serious illness or medical condition that would, in the opinion of theinvestigator, make this protocol unreasonably hazardous. Active infections discoveredduring screening period must be treated and controlled before patient is dosed withVERU-111.
• Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2)caused by previous cancer therapy, excluding alopecia.
• Poor medical risk due to a serious, uncontrolled medical disorder, non-malignantsystemic disease or active, uncontrolled infection. Examples include, but are notlimited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardialinfarction, uncontrolled major seizure disorder, extensive interstitial bilateral lungdisease, or any psychiatric disorder that prohibits obtaining informed consent.
• Total bilirubin levels > 1.5 x ULN (>2.5 x ULN in patients with known Gilbert'sdisease).
• AST and/or ALT levels >2.5xULN or AST and/or ALT levels >1.5xULN WITH concomitantalkaline phosphatase levels >2.5xULN.