Inclusion Criteria: – Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III). Subjects with evidence of metastatic nodal disease to the obuturator or presacral lymph nodes only may be included (N1 M0). Subjects with any degree of fixation of the pelvic sidewall are not eligible. – In Arm 1, subjects must have residual visible tumor following TURBT. In Arm 2, subjects must be fully resected (i.e., no visible tumor or as little tumor as possible) after restaging TURBT 2-6 weeks prior to Study Day 0. – Adequate bone marrow, liver, and renal function, as assessed by the following requirements conducted within 21 days prior to dosing: 1. Hemoglobin ≥ 9.0 g/dL 2. Absolute neutrophil count (ANC) ≥ 1,500/mm3 3. Platelet count ≥ 100,000/mm3 4. Total bilirubin ≤ 1.5xULN (upper limit of normal) 5. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5xULN 6. Glomerular Filtration Rate (GFR) ≥ 30% (≥ 30 ml/min/1.73 m2) – Subjects must be willing to undergo a cystoscopy on study for investigational product removal. – Eligible for and willing to undergo RC per the attending urologist. – Subjects must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist. – Subjects medically eligible for neoadjuvant cisplatin-based combination chemotherapy who refuse this therapeutic option and understand the risks and benefits of doing so. – Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder. – Written informed consent and Health Insurance Portability and Accountability Act of 1966 (HIPAA) authorization for release of personal health information. – Age > 18 years at the time of consent. Exclusion Criteria: – Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome. – Prior systemic chemotherapy for transitional cell carcinoma of the bladder. Any other prior systemic chemotherapy for a non-urothelial carcinoma must have been completed > 5 years prior to initiation of study. – Previous exposure to gemcitabine instillations. – Currently receiving other intravesical chemotherapy. – Concurrent clinically significant infections as determined by the treating investigator. – Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use or removal of TAR-200. – Documented history of vesicoureteral reflux or the presence of an indwelling ureteral stent or nephrostomy tube at the time of screening. – Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥ 6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis. – Bladder Post-Void Residual Volume (PVR) of > 250-mL. – Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection that in the opinion of the investigator, contraindicates participation. Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study. – History or presence of any significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, gynecological, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder that, in the opinion of the investigator, contraindicates participation. – History of diagnosis of neurogenic bladder. – Concomitant immunosuppressive medications, such as methotrexate or TNF inhibitors, within 2 weeks of Study Day 0, exclusive of steroid doses ≤ 5 mg daily. – Difficulty providing blood samples. – Unwilling or unable to provide informed consent or comply with the requirements of this protocol, including the presence of any condition (physical, mental or social) that is likely to affect the subject’s return for scheduled visits and follow-up. – Other unspecified reasons that, in the opinion of the investigator or TARIS, make the subject unsuitable for enrollment.

Main Inclusion Criteria: 1. Patient is at least 18 years of age. 2. Naive or recurrent patients with low grade (LG), non-invasive Upper Tract Urothelial Carcinoma (UTUC) in the pyelocalyceal system. 3. Patient has at least one (1) measurable papillary LG tumor, evaluated visually, ≤ 15 mm. The largest lesion should not exceed 15mm. 4. Biopsy taken from one or more tumors located above the ureteropelvic junction (UPJ) showing LG urothelial carcinoma. Diagnosed not more than 2 months prior to the screening. 5. Patient should have at least one remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm. 6. Wash urine cytology sampled from the pyelocalyceal system documenting the absence of High Grade (HG) urothelial cancer, diagnosed not more than 2 months prior to the screening. 7. Patient with bilateral LG UTUC may be enrolled if at least one side meets the inclusion criteria for the trial and if the other kidney does not require further treatments (The other kidney can be treated prior to the beginning of the study). Main Exclusion Criteria: 1. Patient received Bacille de Calmette et Guérin (BCG) treatment for Urothelial carcinoma (UC) during the 6 months prior to Visit 1. 2. The patient has untreated concurrent urothelial cancer in other locations other than the target area (unless treated during screening) 3. Carcinoma in situ (CIS) in the past in the urinary tract. 4. Patient has a history of invasive urothelial carcinoma in the urinary tract during the past 5 (Five) years. 5. Patient has a history of high grade papillary urothelial carcinoma in the urinary tract during the past 2 (Two) years. 6. Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the trial.

DISEASE CHARACTERISTICS: – Histologically confirmed urothelial carcinoma of the bladder – Stage T2, T3, or T4a disease – No clinical stage consistent with a low-risk of node metastasis (CIS only, T1) – No T4b disease (fixed lesion) – Disease that requires primary radical cystectomy and lymph node dissection for definitive treatment – No laparoscopic surgery – Predominant urothelial carcinoma with any of the following elements allowed: – Adenocarcinoma – Squamous cell carcinoma – Micropapillary or minor components of other rare phenotype – No pure squamous cell carcinoma or adenocarcinoma – No visceral or nodal metastatic disease proximal to the common iliac bifurcation by 2-view chest x-ray and abdominal-pelvic imaging by computerized tomography or MRI of the abdomen and pelvis – No intra-operative pelvic lymph node involvement (confirmed by frozen section) at or above the bifurcation of the common iliac vessels in any of the extended template PATIENT CHARACTERISTICS: – Zubrod performance status 0-2 – ALT and AST ≤ upper limit of normal (ULN)* – Alkaline phosphatase ≤ ULN* – Not pregnant or nursing – Fertile patients must use an effective contraception – No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or stage I or II cancer from which the patient is in complete remission for the past 5 years – Medically suitable to undergo cystectomy, in the physician’s opinion NOTE: *Levels may be ≥ ULN provided metastatic disease is excluded using dedicated liver imaging, bone scan, or biopsy. PRIOR CONCURRENT THERAPY: – See Disease Characteristics – No prior partial cystectomy for invasive bladder cancer – No prior pelvic surgery that would obviate a complete extended lymphadenectomy (e.g., aorto-femoral/iliac bypass) – Prior neoadjuvant chemotherapy for this cancer allowed provided it has been completed and patient has recovered – No prior pelvic irradiation

Inclusion Criteria: – Patients must have histologically proven Ta, carcinoma in situ (CIS) or T1 stage urothelial cell carcinoma of the bladder within 90 days of registration – Patients must have had all grossly visible papillary tumors removed within 30 days prior to registration or cystoscopy confirming no grossly visible papillary tumors within 30 days prior to registration – Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis demonstrating no evidence of metastatic disease (magnetic resonance imaging [MRI] or computed tomography [CT] scan) within 90 days prior to registration; patients with T1 disease must have re-resection confirming =< T1 disease within 90 days prior to registration – Patients must have high-grade bladder cancer as defined by 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification – Patients must not have pure squamous cell carcinoma or adenocarcinoma – Patients’ disease must not have micropapillary components – Patients must have no evidence of upper tract (renal pelvis or ureters) cancer confirmed by one of the following tests performed within 90 days prior to registration: CT urogram, intravenous pyelogram, magnetic resonance (MR) urogram, or retrograde pyelograms – Patients must not have nodal involvement or metastatic disease – No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years; patients with localized prostate cancer who are being followed by an active surveillance program are also eligible – Patients must have a Zubrod performance status of 0-2 – Patients must not have received prior intravesical BCG – Patients must not have known history of tuberculosis – Patients must be PPD negative within 90 days prior to registration; PPD negativity is defined as < 10 mm diameter induration (palpable, raised hardened area) in the volar forearm at 48-72 hours following injection with standard tuberculin dose (5 units, 0.1 ml) – Patients must be >= 18 years of age – Patients must not be taking oral glucocorticoids at the time of registration – Patients must not be planning to receive concomitant biologic therapy, hormonal therapy, chemotherapy, surgery, or other cancer therapy while on study – Prestudy history and physical must be obtained within 90days prior to registration – Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of “reproductive potential” if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, “effective contraception” also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures – Patients must be offered the opportunity to participate in specimen banking for future studies to include translational medicine studies

Inclusion Criteria: – Histologically proven bladder cancer (pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma histologies are excluded). – Stage cT2-T4a N0 M0 disease. – Documented muscle invasive disease with at least one of the following: disease measuring at least 10 mm on cross-sectional imaging OR the presence of tumor-associated hydronephrosis. – Staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest within 56 days prior to registration. If alkaline phosphatase is above the treating institution’s upper limit of normal (ULN), presence of suspicious bone pain, or if other clinical suspicion, a whole body bone scan is required within 56 days prior to registration. – Performance status = 0 or 1 – 18 years of age or older – Must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for COXEN testing and must agree to submission of 20 (10 micron) slides plus 2 (5 micron) slides from the start and end of the 20 slides for a total of 22 unstained slides. – Must agree to collection of tissue (if residual disease is present), urine, and whole blood. – Must agree to participate in the translational medicine studies outlined in the protocol Exclusion Criteria: – Prior systemic cytotoxic chemotherapy or systemic anthracycline – Peripheral neuropathy >/= Grade 2 – Class III/IV heart failure or known left ventricular ejection fraction (LVEF) < 50% – Clinically relevant hearing impairment > Grade 2 – Renal function, calculated creatinine clearance < 60 mL/min – Hepatic function, total bilirubin > 1.5 x institutional upper limit of normal (IULN) (or > 2.5 x IULN with Gilbert’s disease); AST & ALT > 2 X IULN – Hematologic function, absolute neutrophil count (ANC) < 1,500/mcL, hemoglobin < 9 g/dL, and platelets < 100,000/mcL – Hypersensitivity to cisplatin, gemcitabine, doxorubicin, vinblastine, methotrexate, or filgrastim/pegfilgrastim – Incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.) – Pregnant or nursing females – No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. However, patients with localized prostate cancer who are being followed by an active surveillance program are eligible.

Inclusion Criteria: – Adult >18 years old – Suspected or known non-muscle invasive bladder cancer on the basis of a prior cystoscopy Exclusion Criteria: – Porphyria – Gross hematuria – Known hypersensitivity to hexaminolevulinate or aminolevulinate derivatives

Inclusion Criteria: – Pure seminoma after orchiectomy presenting with isolated retropreritoneal lymphadenopathy OR stage I pure seminoma with isolated retroperitoneal relapse. Relapse should be within 3 years – Lymphadenopathy in the retroperitoneum: at least one lymph node 1-3 cm in greatest dimension, no lymph node > 3 cm in greatest dimension, no more than 2 lymph nodes 1-3 cm in greatest dimension – Axial imaging of lymphadenopathy within 6 weeks of the date of RPLND – Retroperitoneal lymphadenopathy must be within the RPLND template – If there is borderline lymphadenopathy, defined as the largest retroperitoneal lymph node measuring 0.90 – 0.99 cm in the greatest dimension, an abdominal computed tomography (CT) scan should be repeated (recommend interval of 6 – 8 weeks); the same lymph node must demonstrate growth to >= 1.0 cm in the greatest dimension – Biopsy is not required, though if biopsy of the retroperitoneal node(s) was obtained, pathology must be consistent with pure seminoma – Chest imaging (x-ray, CT or magnetic resonance imaging [MRI]) negative for metastasis no more than 6 weeks prior to the date of RPLND – Primary tumor excised by radical inguinal orchiectomy and pathology consistent with pure seminoma – Serum alpha fetoprotein (AFP) not more than 1.5 times upper limit of normal, beta-human chorionic gonadotropin (HCG), lactate dehydrogenase (LDH) (per the local laboratory assay) within 14 days of RPLND – Eastern Cooperative Oncology Group (ECOG) performance status =< 1 – Ability to understand and the willingness to sign a written informed consent – Serum coagulation studies (INR/PTT) and platelet counts suitable for surgery per surgeon discretion. Exclusion Criteria: – Second primary malignancy – History of receiving chemotherapy or radiotherapy – Patients receiving any other investigational agent (s) – Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Inclusion Criteria: – Males, aged 40 years to 85, who underwent a previous cancer-negative prostate biopsy within 30 months of being scheduled for a repeat biopsy. – The initial TRUS guided negative prostate biopsy must have collected a minimum of 10 tissue cores and sections from all prostate biopsy cores collected by the physician must be submitted to MDxHealth in order to allow for full comprehensive testing/evaluation of all the sections of the patient’s prostate prior to the scheduled repeat biopsy. – Minimum tissue volume criteria of 20 microns of prostate biopsy core tissue is available (40 microns preferable). – Previous biopsy histology may include the presence of high-grade prostatic intraepithelial neoplasia (HGPIN), proliferative inflammatory atrophy (PIA), glandular inflammation, atypical small acinar proliferation (ASAP) or atypical cells. – Tissue was extracted using standard TRUS guided biopsy core extraction (and not transurethral resection of the prostate (TURP). – Pre-DRE serum sample, pre-DRE plasma sample, and Post-DRE urine sample to be collected in advance of the repeat biopsy. Samples can be collected within three months of the scheduled repeat biopsy, up until the day of, but prior to, the procedure. Exclusion Criteria: – Patient who has undergone previously testing by ConfirmMDx from the same biopsy – Patients with prior diagnosis of prostate cancer in any previous biopsy. – Patients with a limited life expectancy and generally not considered for a repeat Tissue extracted using transurethral resection of the prostate (TURP) procedures – Patients with a history of cancer (except basal cell carcinoma)

Main Inclusion Criteria: 1. Patient is at least 18 years of age. 2. Naive or recurrent patients with low grade (LG), non-invasive Upper Tract Urothelial Carcinoma (UTUC) in the pyelocalyceal system. 3. Patient has at least one (1) measurable papillary LG tumor, evaluated visually, ≤ 15 mm. The largest lesion should not exceed 15mm. 4. Biopsy taken from one or more tumors located above the ureteropelvic junction (UPJ) showing LG urothelial carcinoma. Diagnosed not more than 2 months prior to the screening. 5. Patient should have at least one remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm. 6. Wash urine cytology sampled from the pyelocalyceal system documenting the absence of High Grade (HG) urothelial cancer, diagnosed not more than 2 months prior to the screening. 7. Patient with bilateral LG UTUC may be enrolled if at least one side meets the inclusion criteria for the trial and if the other kidney does not require further treatments (The other kidney can be treated prior to the beginning of the study). Main Exclusion Criteria: 1. Patient received Bacille de Calmette et Guérin (BCG) treatment for Urothelial carcinoma (UC) during the 6 months prior to Visit 1. 2. The patient has untreated concurrent urothelial cancer in other locations other than the target area (unless treated during screening) 3. Carcinoma in situ (CIS) in the past in the urinary tract. 4. Patient has a history of invasive urothelial carcinoma in the urinary tract during the past 5 (Five) years. 5. Patient has a history of high grade papillary urothelial carcinoma in the urinary tract during the past 2 (Two) years. 6. Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the trial.

Inclusion Criteria: – Undergoing elective open radical cystectomy – Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: – Allergy or adverse reaction to ropivacaine (ropivacaine hydrochloride) or any amide type of local anesthesia – Allergy or adverse reaction to local anesthesia catheter – Additional surgery at the same time as RC (e.g. nephroureterectomy) – Coagulopathy – Thrombocytopenia – Local or systemic infection – Pregnancy – Chronic hepatic disease – Use of type III antiarrhythmics (e.g. amiodarone) – History of chronic pain and/or daily opioid use

Inclusion Criteria: – Indication for radical cystectomy for urothelial cancer – All types of urinary diversions – Tis-T3 Urothelial cancer; patients will be stratified according to clinical stage – Ability to consent – Patient meets criteria to be a surgical candidate Exclusion Criteria: – Inability to give consent or adhere to follow-up schedule – T4 tumor – Bulky lymphadenopathy (> 2 cm) – Prior pelvic radiation – Not surgical candidate because of significant co-morbidity – Uncontrolled coagulopathy

Inclusion Criteria: – Bladder cancer, undergoing radical cystectomy and ileal conduit diversion – Ability to understand and the willingness to sign a written informed consent – Follow-up either here at University of Southern California (USC) or centers that are available to transfer the requested clinical and radiological data Exclusion Criteria: – Previous scar or mesh at the level of ileal conduit – Survival less than 12 months after surgery (either predicted survival before surgery or actual survival after surgery < 12 months) – History of allergic reactions attributed to compounds of similar chemical or biologic composition to cadaveric component, i.e. Flex HD

Key Inclusion Criteria: – Urinary Incontinence for at least 3 months prior to Screening as a result of Neurogenic Detrusor Overactivity due to Spinal Cord Injury or Multiple Sclerosis. – Subjects with Spinal Cord Injury must have a stable neurological injury at T1 level or below which occurred at least 6 months prior to Screening. – Subjects with Multiple Sclerosis must be clinically stable in the investigator’s opinion, with no exacerbation (relapse) of MS for at least 3 months prior to Screening. – Subjects must have had an inadequate response after at least 4 weeks of oral medications used in the treatment of NDO (e.g. anticholinergics, beta-3 agonists) and/or have intolerable side-effects. – Routinely performing Clean Intermittent Catheterization (CIC) to ensure adequate bladder emptying. – An average of at least two episodes per day of Urinary Incontinence recorded on the screening bladder diary. Key Exclusion Criteria: – Any current condition (other than NDO) that may impact on bladder function. – Previous or current, tumour or malignancy affecting the spinal column or spinal cord, or any other unstable cause of SCI. – Any condition that will prevent cystoscopic treatment administration or CIC usage, e.g. urethral strictures. – Current indwelling bladder catheter, or removal of indwelling bladder catheter less than 4 weeks prior to Screening. – BTX-A treatment within 9 months prior to Screening for any urological condition (e.g. detrusor or urethral sphincter treatments). – Any neuromodulation/electrostimulation usage for urinary symptoms/incontinence within 4 weeks prior to Screening. Any implanted neuromodulation device must be switched off at least 4 weeks prior to Screening.

Inclusion Criteria: – Male; 18 years of age and older – Histopathologically proven adenocarcinoma, Gleason grade ≥ 7 of the prostate planned radical prostatectomy; appropriate for treatment with paclitaxel therapy – ECOG of 0 or 1 – Laboratory requirements: – WBC >2500/mm3 – Neutrophil >1500/mm3 – Hemoglobin >10 mg/dL – Platelet >100,000/ mm3 – AST and ALT <2.5 x ULN – Total bilirubin <1.5 x ULN – Creatinine <2 mg/dL – Normal PT/INR and PTT; – Willing to use appropriate contraception from time of NanoPac® injection until prostatectomy – Willing to receive an mpMRI Exclusion Criteria: – Evidence of locally advanced or metastatic disease; – Prostate size ≥ 50 cc – Prior prostatectomy – Anticipated use of concomitant chemotherapy (other than the protocol specified agents), immunotherapy, or systemic use of hormonal therapy (such as GnRH analogs, antiandrogens, androgen receptor inhibitors, and 5-α reductase inhibitors) prior to surgery – Treatment with a prior investigational agent within 30 days of first dose of investigational medication – Any previous local treatment of the prostate (i.e. radiation) – Any other condition (e.g. psychiatric disorder) that, in the opinion of the Investigator, may interfere with the patient’s ability to comply with the study requirements or visit schedule – Known sensitivity to any of the study medication components – History of prior malignancy that has not been in remission for >5 years, with the exception of basal cell or squamous cell carcinoma.

Inclusion Criteria: – Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information – Note: HIPAA authorization may be included in the informed consent or obtained separately – Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 within 3 months (93 days) prior to being registered for protocol – African-American or white men (Hispanic or non-Hispanic) – Prostate biopsy-naive or a single negative biopsy – Having elevated prostate specific antigen (PSA) (> 2.5 ng/ml) and no palpable nodule on digital rectal exam (DRE) – Ability to understand the willingness to sign a written informed consent – Patients must be willing to undergo a radiologic imaging before and after biopsy of the prostate – Patients must be willing to undergo a biopsy of the prostate Exclusion Criteria: – Patients who have had chemotherapy or radiotherapy within 12 months of the study for other diagnoses not related to prostate cancer – Patients receiving any other investigational agents – Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements – Patients with active inflammatory bowel disease – Patients who are unable to undergo MRI – Patients who had any surgery of the prostate including TURP (transurethral resection of the prostate) – Patients who had > 1 prior prostate biopsy

Inclusion Criteria: – Male having a diagnosis of clinically-significant prostate cancer (CsPCa) made within the past 12 months (Gleason 7-9) with no evidence of metastatic disease; all outside pathology will be re-reviewed at University of Southern California (USC) to verify diagnosis – Patients have elected to undergo radical prostatectomy (RP) as treatment of choice and have to be a surgical candidate for RP; this determination will be made by the patient in conjunction with their treating urologist and is current standard of practice – Standard preoperative evaluation is performed and deemed satisfactory to proceed to surgery as per their treating urologist – Ability to understand AND willingness to sign a written informed consent – Patients must be willing to undergo HIFU, CEUS, MRI and prostate biopsy pre-RP for research purposes Exclusion Criteria: – Patients may not be receiving any other investigational agents or have received any definitive prostate cancer (PCa)-specific treatment (en-bloc resection of bladder tumors [EBRT], Brachytherapy etc) prior – Patients with known metastases would be excluded from this clinical trial – Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinical significant cardiac arrhythmia (rate controlled atrial fibrillation allowed), or psychiatric illness/social situations that would limit compliance with study requirements – Patients with active autoimmune diseases or active immune suppressive therapy or inflammatory bowel disease; a low dose steroid daily administration (equivalent dexamethasone < 10mg/day) is acceptable – Patients with rectal disease – Patients who are unable to undergo MRI – Patients with convincing evidence of extraprostatic extension or T4 disease on digital rectal examination (DRE)

Inclusion Criteria: – Male having a diagnosis of clinically-significant prostate cancer (CsPCa) made within the past 12 months (Gleason 7-9) with no evidence of metastatic disease; all outside pathology will be re-reviewed at University of Southern California (USC) to verify diagnosis – Patients have elected to undergo radical prostatectomy (RP) as treatment of choice and have to be a surgical candidate for RP; this determination will be made by the patient in conjunction with their treating urologist and is current standard of practice – Standard preoperative evaluation is performed and deemed satisfactory to proceed to surgery as per their treating urologist – Ability to understand AND willingness to sign a written informed consent – Patients must be willing to undergo HIFU, CEUS, MRI and prostate biopsy pre-RP for research purposes Exclusion Criteria: – Patients may not be receiving any other investigational agents or have received any definitive prostate cancer (PCa)-specific treatment (en-bloc resection of bladder tumors [EBRT], Brachytherapy etc) prior – Patients with known metastases would be excluded from this clinical trial – Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinical significant cardiac arrhythmia (rate controlled atrial fibrillation allowed), or psychiatric illness/social situations that would limit compliance with study requirements – Patients with active autoimmune diseases or active immune suppressive therapy or inflammatory bowel disease; a low dose steroid daily administration (equivalent dexamethasone < 10mg/day) is acceptable – Patients with rectal disease – Patients who are unable to undergo MRI – Patients with convincing evidence of extraprostatic extension or T4 disease on digital rectal examination (DRE)

Inclusion Criteria: – Subjects must meet the criteria for one of the three following groups: – Normal patients- aged 40 years and older with no evidence of hematuria or cancer – Patients with localized bladder cancer diagnosed by cystoscopy and pathology: T2N0M0 or T3N0M0 who have not received neoadjuvant chemotherapy – Patients with metastatic bladder cancer: newly diagnosed with no previous treatment for metastatic disease – Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: – For normal subject arm: evidence of cancer or hematuria – For localized bladder cancer: evidence of metastatic disease, second cancer, prior chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier – For metastatic bladder cancer: prior therapy for metastatic disease – Uncontrolled intercurrent illness including, but not limited to previous or current history of second malignancy unrelated to bladder cancer; autoimmune disease or immune deficiency, chronic treatment with immunomodulatory therapies (e.g. glucocorticoids); significant trauma, surgery, or infection in the past two weeks or psychiatric illness/social situations that would limit compliance with study requirements

Inclusion Criteria: – Subjects enrolled in this study must meet one of the 3 following criteria: – Group 1: Healthy individual with no history of cancer or hematuria – Group 2: Subject with a diagnosis of localized renal cell carcinoma (by imaging and eventual pathology) scheduled to undergo nephrectomy – Group 3: Subject with a diagnosis of metastatic renal cell cancer(by imaging and eventual pathology) who is scheduled to begin a new systemic therapy – Any type of renal cell carcinoma (RCC); any prior therapy – Performance status: 0-3 – Leukocytes >= 3,000/mcL (frequently used – numbers listed are examples, investigator should modify as needed) – Absolute neutrophil count >= 1,500/mcL (frequently used – numbers listed are examples, investigator should modify as needed) – Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: – For normal subject arm: no evidence of cancer or hematuria – For localized RCC arm: no evidence of metastatic disease, second cancer, prior chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier – For metastatic RCC arm: no evidence of second cancer, prior chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier – For all subjects: uncontrolled intercurrent illness including, but not limited to previous or current history of second malignancy unrelated to renal cell carcinoma; autoimmune disease or immune deficiency, chronic treatment with immunomodulatory therapies (e.g. glucocorticoids); significant trauma, surgery, or infection in the past two weeks or psychiatric illness/social situations that would limit compliance with study requirements

Inclusion Criteria: – A diagnosis of histologically confirmed prostate adenocarcinoma and falling into one of the following 5 groups: – Currently receiving ADT (previously untreated for metastatic disease) – These patients will be grouped into 3 cohorts: having received ADT for 3-6 months; for 1-2 years; and for > 3 years – Scheduled to begin treatment with ADT (previously untreated for metastatic disease) – Scheduled to begin treatment with enzalutamide (castration resistant / has received ADT / may have received abiraterone) – Scheduled to begin treatment with abiraterone (castration resistant / has received ADT / may have received enzalutamide) – Scheduled to begin treatment with docetaxel (castration resistant / has received ADT / has received enzalutamide and/or abiraterone) – Have been diagnosed with either hormone-naive or castrate-resistant metastatic disease – Ability and willingness to provide written and informed consent Exclusion Criteria: – Patients who receive combined ADT with docetaxel for hormone-naive metastatic prostate cancer – Patients on intermittent ADT

Inclusion Criteria: – ELIGIBILITY CRITERIA FOR RANDOMIZATION: – Patients must have a renal mass consistent with a clinical stage >= T2Nx renal cell carcinoma (RCC) or TanyN+ RCC for which radical or partial nephrectomy is planned – Patients must have no clinical or radiological evidence of distant metastases (M0) unless the presumed M1 disease is planned to be resected/definitively treated (e.g., thermal ablation, stereotactic radiation) at the same time or up to 12 weeks after the date of the initial procedure such that the patient is considered “no evidence of disease” (M1 NED) – Liver, bone, or brain metastases are not permitted – No more than 3 metastases are permitted, and all must be able to be removed or definitively treated within 12 weeks of the primary tumor resection – If histological confirmation of RCC has not been done within 12 months prior to randomization, patient must be willing to undergo a core biopsy for this purpose if randomized to Arm A – NOTE: This histologic confirmation can be a (1) standard of care diagnostic biopsy or (2) a research biopsy or a planned metastasectomy. Tissue must be obtained with results available prior to the neoadjuvant dose – Patients randomized to Arm A: core tumor biopsy must have demonstrated RCC of any histology, including sarcomatoid, unclassified, or “unknown histology” (if preoperative biopsy was uninformative) with exception below for non-diagnostic biopsies – If the biopsy performed following randomization clearly demonstrates a benign condition, oncocytoma or a different type of cancer that is not RCC, the patient is not eligible and must come off study – A non-diagnostic biopsy is considered a good faith effort and does not need to be repeated unless deemed clinically necessary by the treating investigator – Patient must not have any prior systemic or local anti-cancer therapy for the current RCC – Patient must not have undergone a partial nephrectomy for the current RCC – Patient must not have had a metastasectomy for the current RCC diagnosis unless performed to render patient NED (in addition to the planned nephrectomy) within 6 months prior to the current diagnosis – Patient must not have received current or past antineoplastic systemic therapies for RCC: i.e., chemotherapy, hormonal therapy, immunotherapy, or standard or investigational agents for treatment of RCC – Patient must not have received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways – Patient must be >= 18 years of age. Because no dosing or adverse event data are currently available on the use of nivolumab therapy in patients < 18 years of age, children are excluded from this study – Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 – Patient must not have a prior history of RCC that was treated with curative intent within the past 5 years – Patients with a prior RCC that was treated > 5 years before, are eligible if the current tumor is consistent with a new primary in the opinion of the treating investigator – Patients with bilateral synchronous RCCs are eligible if they can be resected or definitively treated at the same time or within a 12 week window from time of initial nephrectomy (partial or radical) or procedure and maintain adequate residual renal function; the patient is not eligible if both kidneys are to be completely removed and subsequent hemodialysis will be required – Permitted forms of local therapy for second tumor: – Partial or radical nephrectomy – If kidney tumor is =< 3 cm: thermal ablation (e.g., radiofrequency ablation, cryoablation or stereotactic radiosurgery) – Patients cannot have concurrent malignancies, with the following exceptions: – Adequately treated basal cell or squamous cell skin cancer – In situ cervical cancer – A history of superficial Ta urothelial cancer is permitted (as long as not currently undergoing treatment) whereas T1 or greater disease is excluded if < 3 years from diagnosis; concurrent persistent disease is not permitted – Adequately treated stage I or II cancer from which the patient is currently in complete remission – Any other cancer and stage from which the patient has been disease-free for at least 3 years prior to the time of randomization and as long as they are not receiving any current treatment (e.g. adjuvant or maintenance systemic or local therapy) – Concurrent low risk prostate cancer on active surveillance – Patient must not have active known or suspected autoimmune disease. The following autoimmune disorders are permitted: patients with vitiligo, type I diabetes mellitus, controlled/stable hypo or hyperthyroidism due to autoimmune or non-autoimmune conditions (hormone replacement is allowed), psoriasis not requiring systemic treatment, or other conditions not expected to recur – Patient must not have any ongoing condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications with the exceptions outlined below; patient must not have received any treatment with other immunosuppressive agents within 14 days prior to the first dose of study drug with the following exceptions: – Topical, ocular, intra-articular, intranasal, inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone or the equivalent are permitted in the absence of active autoimmune disease – A brief (less than 3 weeks) course of corticosteroids (any amount) for prophylaxis (for example: contrast dye allergy) or for treatment of non-autoimmune conditions (for example: nausea, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted – Patient must not have uncontrolled adrenal insufficiency – Patient must not have known evidence of chronic active liver disease or evidence of acute or chronic hepatitis B Virus (HBV) or hepatitis C (HCV); HBV and HCV testing must be completed within 8 weeks prior to randomization – NOTE: If the patient has been treated and cured, and the HCV ribonucleic acid (RNA) is undetectable, the patient is eligible for this study – Patient must not have any serious intercurrent illness, including ongoing or active infection requiring parenteral antibiotics – Patient must not have known evidence of human immunodeficiency virus (HIV) infection, since the effects of nivolumab on anti-retroviral therapy have not been studied; HIV testing is only required if past or current history is suspected – Patient must not have any known medical condition (e.g. a condition associated with uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the investigator’s opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results – Patient must not have had any major surgery within 28 days prior to randomization – Patient must not be currently enrolled in other clinical trials testing a therapeutic intervention – Patient must not have any history of severe hypersensitivity to a monoclonal antibody – Patient must have the ability to understand and the willingness to sign a written informed consent document – Patients must not be pregnant or breast-feeding, as the effects of nivolumab on the developing human fetus or in the nursing infant are unknown; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a patient of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) – Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception, as described in the informed consent form (ICF), or by abstaining from sexual intercourse for the duration of their participation in the study; patients of childbearing potential must use adequate methods to avoid pregnancy for 5 months after the last dose of nivolumab – White blood cells >= 2000/uL (within 8 weeks prior to randomization) – Absolute neutrophil count (ANC) >= 1,500/mm^3 (within 8 weeks prior to randomization) – Platelet count >= 100,000/mm^3 (within 8 weeks prior to randomization) – Hemoglobin >= 9.0 g/dL (within 8 weeks prior to randomization) – Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) >= 40mL/min (within 8 weeks prior to randomization) – Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 x ULN) (within 8 weeks prior to randomization) – Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 8 weeks prior to randomization)

Inclusion Criteria: 1. Locally advanced unresectable or metastatic stage 4 (i.e. T4 or N3 or M1) PSCC 2. Radiologic evidence for progressive disease after ≥1 prior chemotherapy regimen 3. Be at least 18 years of age on day of signing informed consent. 4. Have measurable disease based on RECIST 1.1. 5. Have a performance status of 0-2 on the ECOG (Eastern Cooperative Oncology Group) Performance Scale. 6. Demonstrate adequate organ function with all screening labs being performed within 14 days of treatment initiation. – Absolute neutrophil count (ANC) ≥1,500 /mcL – Platelets ≥100,000/mcL – Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment) – Serum creatinine ≤1.5 X upper limit of normal (ULN); alternately measured or calculated creatinine clearance ≥30 mL/min with creatinine levels >1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl) – Serum total bilirubin ≤1.5 X ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels >1.5 ULN – AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN or ≤ 5 X ULN for subjects with liver metastases – Albumin >2.5 mg/dL – International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants – Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 7. Subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy 8. Formalin-fixed paraffin embedded (FFPE) tumor tissue from previous biopsy is requested, but not mandatory. 9. Be willing and able to provide written informed consent/assent for the trial. Exclusion Criteria: 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 3. Has a known history of active TB (Bacillus Tuberculosis) 4. Hypersensitivity to Pembrolizumab or any of its excipients. 5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. – Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. – Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 10. Has known history of, or any evidence of active, non-infectious pneumonitis. 11. Has an active infection requiring systemic therapy. 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 14. Is pregnant expecting to father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 18. Has known active Tuberculosis infection. 19. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Inclusion Criteria: – Be willing and able to provide written informed consent/assent for the trial – Advanced (metastatic or recurrent) pathologically proven urothelial carcinoma which is refractory to platinum based due to disease progression on a platinum containing regimen; patients progressing within 12 months of their last dose of platinum-based neoadjuvant or adjuvant chemotherapy will be considered platinum refractory – Have measurable disease based on RECIST 1.1 – Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained for up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor; an optional core biopsy will be requested from an accessible metastatic site after 2 cycles of treatment – Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale – Absolute neutrophil count (ANC) >= 1,500/mcL – Platelets >= 100,000/mcL – Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) – Measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30mL/min for subject with creatinine levels > 1.5 X institutional upper limit of normal (ULN) – Serum total bilirubin =< 1.5 X ULN or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN – Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN or =< 5 X ULN for subjects with liver metastases – Albumin >= 2.5 mg/dL – International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants – Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants – Recovered to grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies – Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required – Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year – Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Exclusion Criteria: – Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment – Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment – Has a known history of active TB (bacillus tuberculosis) – Hypersensitivity to pembrolizumab or any of its excipients – Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (ie, =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier – Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (ie, =< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy – Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin or early stage carcinoma of the cervix that has undergone potentially curative therapy or in situ cervical cancer; patients with incidental prostate cancer diagnosed at cystectomy or deemed appropriate for surveillance based on national guidelines will be allowed to enroll – Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability – Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment – Has known history of, or any evidence of active, non-infectious pneumonitis – Has an active infection requiring systemic therapy – Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator – Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial – Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment – Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or sEsphB4-HSA – Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) – Has known active Hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C (eg, hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) – Major systemic infection requiring antibiotics 72 hours or less prior to first dose of study drug – Has New York Heart Association (NYHA) class 3 or 4, myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEphB4HSA or pembrolizumab (MK-3475) or places the patient at undue risk for treatment related complications – Any other condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results – Any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesis – Has received a live vaccine within 30 days of planned start of study therapy; Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, flu-mist) are live attenuated vaccines, and are not allowed