• Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC
• Has received no prior systemic therapy for advanced RCC; prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed ≥12 months before randomization/allocation
• Is able to swallow oral medication
• Has adequate organ function
• Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation
• Has resolution of toxic effects of the most recent prior therapy to ≤Grade 1
• If participants receive major surgery or radiation therapy, they must have recovered from complications from the intervention
• Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation
• Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab or a combination of the aforementioned drugs, no contraception is needed
• Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab for 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last
• Has urine protein ≥1 g/24 hours and has any of the following: (a) hypoxia defined as a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen
• Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration
• Has had major surgery within 3 weeks before first dose of study interventions
• Has a history of lung disease
• Has a history of inflammatory bowel disease
• Has preexisting gastrointestinal (GI) or non-GI fistula
• Has malabsorption due to prior GI surgery or disease
• Has received prior radiotherapy within 2 weeks of start of study intervention
• Has received a live or live attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
• Has received more than 4 previous systemic anticancer treatment regimens
• Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B
• Has had an allogenic tissue/solid organ transplant

• Normal Body Mass Index (≥ 18.5 to < 25); Obese Body Mass Index (≥ 30 to ≤ 45)
• Able to provide informed consent
• Willingness to consume controlled diet
• Composition of most recent stone > 50% calcium oxalate, no uric acid component
• First time or recurrent calcium oxalate stone former
• 24-hour urine collections with creatinine values within 20% of appropriate ratio of creatinine (mg)/body weight (kg) for gender, and with creatinine values that are consistent between collections (within 20% of each other)
• Willingness to stop supplements [vitamins, Ca (citrate or carbonate) and other minerals, herbal supplements, nutritional aids, probiotics] for 14 days before start and during study
• Willingness to not undertake vigorous exercise during the controlled dietary study
• Normal fasting blood Comprehensive Metabolic Panel
• Hemoglobin A1c < 6.5%
• No food allergies or intolerance to any of the food in study menus
• Permitted/willing to discontinue medications for kidney stone prevention, including thiazides, allopurinol, and febuxostat and citrate preparations, for 14 days before start and during the studies. They will be instructed to restart these medications at the conclusion of the study
• Diabetes
• Abnormal fasting comprehensive metabolic panel (CMP)
• Hemoglobin A1c (HbA1c) result ≥ 6.5%
• Gout
• Estimated Glomerular Filtration Rate (eGFR) <60 ml/min/1.73m^2
• Primary hyperoxaluria
• Cystic fibrosis
• Cystinuria
• Uric acid stone former
• Utilization of immunosuppressive medication
• Nephrotic syndrome
• Enteric hyperoxaluria
• Gastrointestinal disorder that could impact oxalate transport
• Sarcoidosis
• Uncontrolled hypertension
• Renal tubular acidosis
• Primary hyperparathyroidism
• Liver disease
• Neurogenic bladder
• Urinary diversion
• Chronic diarrhea
• Bariatric surgery
• Active malignancy or treatment for malignancy within 12 months prior to screening
• Pregnancy
• Breast feeding/nursing
• Females of child bearing age who are not able to use an effective method of birth control during the study
• Mental/medical condition that is likely to impede successful study completion
• Illness including flu / common cold / fever 14 days before study and during study
• Diarrhea or other abnormal gastrointestinal event (e.g. abnormal bowel movements) 14 days before study or during study
• Antibiotic use within last 6 months (based on recommendations of the NIH Human Microbiome Project, Protocol A)
• Inability or unwillingness to undergo MRI

1. 1 month of age up to < 18 years of age at the time of signing the informed consent. 2. Received HSCT within the past 6 months. 3. Diagnosis of TMA that persists despite initial management of any triggering condition. 4. Body weight ≥ 5 kilograms. 5. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception starting at Screening and continuing until at least 8 months after the last dose of ravulizumab. 6. Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b and Streptococcus pneumoniae if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. All participants should be administered coverage with prophylactic antibiotics according to institutional post-transplant infection prophylaxis guidances, including coverage against Neisseria meningitidis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis the entire Treatment Period and for 8 months following the final dose of ravulizumab. 1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' deficiency (activity < 5%). 2. Known Shiga toxin-related hemolytic uremic syndrome. 3. Positive direct Coombs test. 4. Diagnosis or suspicion of disseminated intravascular coagulation. 5. Known bone marrow/graft failure. 6. Diagnosis of veno-occlusive disease. 7. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer). 8. Unresolved meningococcal disease. 9. Presence or suspicion of sepsis (treated or untreated) within 7 days prior to Screening. 10. Pregnancy or breastfeeding. 11. Hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab. 12. Previously or currently treated with a complement inhibitor.

The main inclusion and exclusion criteria include but are not limited to the following:
• Has a histologically or cytologically confirmed diagnosis of RCC with clear cell component per American Joint Committee on Cancer (AJCC) (8th Edition), with or without sarcomatoid features
• Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node metastasis and tumor grading: 1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0 2. High risk RCC: pT4, any Grade N0, M0; pT any stage, any Grade, N+, M0 3. M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤2 years from nephrectomy (metachronous)
• Has undergone complete resection of the primary tumor (partial or radical nephrectomy) and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants
• Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to randomization
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days before randomization.
• Male participants must agree to continue contraception at least 7 days after the last dose of belzutifan/placebo
• Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of pembrolizumab or at least 30 days after last dose of belzutifan/placebo, whichever occurs last
• Has adequate organ function
• Has had a major surgery, other than nephrectomy plus resection of preexisting metastases for M1 NED participants, within 4 weeks prior to randomization
• Has a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
• Has clinically significant cardiovascular disease within 6 months from first dose of study intervention
• Has other clinically significant disorders such as: serious active nonhealing wound/ulcer/bone fracture; requirement for hemodialysis or peritoneal dialysis
• Has preexisting brain or bone metastatic lesions
• Has received prior systemic therapy for RCC
• Has received prior radiotherapy for RCC
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention; administration of killed vaccines are allowed
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has a known additional malignancy (other than RCC treated with nephrectomy and/or metastasectomy) that is progressing or has required active treatment within the past 3 years
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy is allowed
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection, requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection, a known history of Hepatitis B or known active Hepatitis C virus infection
• Has had an allogenic tissue/solid organ transplant

1. Histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma. 2. Must have received prior treatment with an immune checkpoint inhibitor (CPI). 3. Subjects must have received prior treatment with platinum-containing chemotherapy. 4. Subjects must have had progression or recurrence of urothelial cancer. 5. Subjects must have measurable disease according to RECIST (Version 1.1). 6. Adequate bone marrow function. 7. Adequate renal function. 8. Adequate liver function. 9. Adequate Eastern Cooperative Oncology Group (ECOG) performance status. 1. Preexisting sensory or motor neuropathy Grade ≥2. 2. Presence of symptomatic or uncontrolled central nervous system (CNS) metastases. 3. Prior treatment with enfortumab vedotin or other monomethylauristatin (MMAE)-based antibody-drug conjugate (ADCs) 4. Prior treatment with any anti-CD47 or anti-signal regulatory protein-α (SIRPα) agent. 5. Known active keratitis or corneal ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated. 6. History of uncontrolled diabetes mellitus within 3 months of the first dose of study drug.

Inclusion Criteria 1. Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor. 2. Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible) 3. All brain metastases must be outside the brain stem (midbrain, pons and medulla). 4. Patient must have 10 or less brain metastases. 5. The maximum diameter of any lesion must be less than or equal to 3.0 cm. 6. Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS 7. Age ≥ 18 years. 8. ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better. 9. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Medically acceptable birth control (contraceptives) includes:
• Approved hormonal contraceptives (such as birth control pills, patch, or ring: Depo-Provera, Implanon), or
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a substance that kills sperm) 10. Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria 1. Patients had craniotomy and surgery to the brain within 7 days from the date of SRS. 2. Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion. 3. Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast) 4. Patients with life expectancy < 3 months. 5. 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, in the opinion of the investigator, would limit compliance with study requirements. 6. Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

• infants/ children with midshaft or distal hypospadias undergoing primary single stage repair in one of the Pediatric Regional Anesthesia Network participating centers.
• prior hypospadias surgery,
• proximal or penoscrotal hypospadias,
• abnormal caudal anatomy or spinal dysraphism,
• cyanotic congenital heart disease,
• infection or rash at the block injection site.

• Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder
• Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
• Has provided tissue for biomarker analysis
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Has adequate organ function
• During the treatment period and for ≥7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic
• Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for ≥7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last BCG Post-induction Cohort (Cohort A) Only
• Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
• Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC
• Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
• Has concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC
• Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment
• Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
• Has an active infection or diagnosis requiring systemic antimicrobial therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has current active tuberculosis
• Has had an allogenic-tissue/solid organ transplant
• Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed BCG Post-induction Cohort (Cohort A) Only
•Has persistent T1 disease following an induction course of BCG BCG Naïve Cohort (Cohort B) Only
•Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry

• Patients with newly diagnosed stages 2
•4 diffuse anaplastic Wilms tumor must be enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an eligibility requirement for patients with relapsed favorable histology Wilms tumor.
• Patients must be =< 30 years old at study enrollment
• Patients with the following diagnoses are eligible for this study:
• Newly diagnosed stages 2
•4 diffuse anaplastic Wilms tumor as confirmed by central review
• Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must have previously achieved remission for their initial FHWT diagnosis to be eligible for this study. The relapse risk groups are defined as follows, regardless of radiation therapy:
• Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine
• High-Risk relapse: Patients who received three chemotherapy agents for frontline therapy; primarily vincristine, actinomycin D and doxorubicin or vincristine, actinomycin D and irinotecan
• Very High-Risk relapse: Patients who received four or more chemotherapy agents as part of initial therapy; primarily regimen M or its variations
• Patients with newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required
• Note: For relapsed FHWT patients, an institutional pathology report confirming favorable histology Wilms tumor (from relapse, if available, or from original diagnosis) must be available for upload prior to initiation of protocol therapy
• Patients with newly diagnosed Stages 2
•4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review of the initial biopsy
• Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Patients must have a life expectancy of >= 8 weeks
• Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have had no prior systemic therapy, except in the following situations:
• Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks of pre nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms tumor at delayed nephrectomy
• Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for presumed favorable histology Wilms tumor based on institutional review, but subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2 initial risk assignment results (if available per current version of AREN03B2)
• Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an emergent basis and within allowed timing as described
• Note: Patients who received prior therapy for presumed favorable histology Wilms tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who received emergency radiation to preserve organ function are eligible as noted. Patients who received radiation as part of standard of care for presumed newly diagnosed favorable histology Wilms tumor, along with chemotherapy as noted above, prior to identification of diffuse anaplasia, are also eligible
• Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In addition, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study
• Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who received emergency radiation to preserve organ function are eligible and do not need to washout with the above criteria
• Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment)
• Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to enrollment)
• Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed within 7 days prior to enrollment)
• Patients with high-risk or very high-risk relapsed FHWT who will be treated with regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or radioisotope glomerular filtration rate (GFR) and meet the following requirement:
• Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within 7 days prior to enrollment)
• Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR (meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum creatinine as per the following table:
• Age: Maximum Serum Creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 0.6 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =< ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases (performed within 7 days prior to enrollment)
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram (obtained within 21 days prior to enrollment and start of protocol therapy)
• Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
• Patients with any uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, or symptomatic congestive heart failure (defined as grade 2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
• Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk FHWT initially observed without chemotherapy) or received only one chemotherapy agent for frontline therapy
• For patients with high-risk or very high-risk relapsed FHWT:
• Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16 mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation
• For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
• Chronic inflammatory bowel disease and/or bowel obstruction
• Concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

1. Ages 6 to 17 years (inclusive); 2. Estimated GFR of 15-59 ml/min per 1.73 m2 by modified CKiD formula;56 3. Serum phosphate within age appropriate normal levels; 4. Serum ferritin <500 ng/ml and TSAT <50%; 5. For those patients treated with growth hormone, calcitriol, nutritional vitamin D, iron, and/or ESAs such treatments must have stable dosing for at least 2 weeks prior to screening; 6. Able to swallow tablets; 7. Able to eat at least two meals a day; 8. In the opinion of the investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations. 1. Perform physical exam and obtain vitals. 2. Check urine pregnancy test in menstruating female participants and administer corresponding questionnaire. 3. Administer GI Symptom questionnaire. 4. Ascertain AEs. 5. Obtain information on concomitant medications. 6. Process 24-hour urine sample for 24 hour urine creatinine and phosphate. 7. Measure run-in adherence using eCAP system and pill count. 8. Administer the Medical Adherence Measure tool. 9. Reinforce adherence. 10. Prepare one month's supply of drug and enter them into eCAP system.

• Adult (>18 years) recipients of a kidney-only transplant, including re-transplants
• Non-HLA identical Living or Deceased Donor Grafts
• Able to provide informed consent
• Absence of donor specific antigens
• Stable renal function (eGFR>40mL/min for 3 months prior to enrollment)
• Patients treated with Belatacept as part of de novo immunosuppression or converted to Belatacept with stable kidney function for 3 months (as stated above)
• Patients who underwent kidney transplantation at least 9 months prior to study entry
• Prior or concurrent non-kidney organ transplants
• Presence of BK nephropathy in current graft
• Recipient on any other investigational drug in the 12 weeks prior to inclusion
• Patient with history of recent (<3mo), recurrent, or severe (Banff Grade 2 or greater or unable to be treated with steroids) acute rejection episodes
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial
• Significant hepatic impairment
• Bilateral kidney transplantation
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

• Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug Administration (FDA)-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI). Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
• Patients who have previously received other forms of immunotherapy (high-dose [HD] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
• Age >= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky >= 60)
• Life expectancy of greater than 12 weeks
• Leukocytes >= 1,000/mcL
• Absolute neutrophil count >= 500/mcL
• Platelets >= 50,000/mcL
• Total bilirubin =< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional ULN or < 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
• Creatinine ULN OR glomerular filtration rate (GFR) >= 30 mL/min (if using the Cockcroft-Gault formula)
• Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
• If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
• If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
• The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), if all of the following criteria are met:
• Repeat imaging demonstrates no new sites of bone metastases
• The lesion being considered for palliative radiation is not a target lesion
• Patients with prior therapy with an anti-PD-1 or anti-PD-L1
• Patients with prior allogeneic hematologic transplant
• Patients who are receiving any other anticancer 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 who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) bleeding, obstruction, and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. For the IBD (UC and CD) cohort, an endoscopic assessment, disease activity index, and disease specific inclusion/exclusion criteria will substitute for these factors in determining eligibility with the exception of abdominal carcinomatosis, which should prompt further evaluation

• Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC
• Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a PD-(L)1 checkpoint inhibitor (in sequence or in combination with a vascular endothelial growth factor
•tyrosine kinase inhibitor [VEGF-TKI]) where PD-(L)1 checkpoint inhibitor treatment progression is defined by meeting ALL of the following criteria: (a) has received ≥2 doses of an anti-PD-(L)1 monoclonal antibody (mAb) (b) has shown radiographic disease progression during or after an anti-PD-(L)1 mAb as defined by RECIST 1.1 by investigator (c) disease progression has been documented within 12 weeks from the last dose of an anti-PD-(L)1 mAb
• Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a VEGF-TKI (in sequence or in combination with a PD-[L]1 checkpoint inhibitor) where VEGF-TKI treatment progression is defined by meeting the following criterion: has shown radiographic disease progression during or after a treatment with a VEGF-TKI as defined by RECIST 1.1 by investigator
• Is able to swallow oral medication
• Has adequate organ function
• Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation
• Has resolution of toxic effects of the most recent prior therapy to ≤Grade 1
• If participants receive major surgery or radiation therapy, they must have recovered from complications from the intervention
• Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation
• Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, MK-4830 or a combination of the aforementioned drugs, no contraception is needed
• Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, MK-4830 or 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last
• Has urine protein ≥1 g/24 hours and has any of the following: (a) hypoxia defined as a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen
• Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration
• Has had major surgery within 3 weeks before first dose of study interventions
• Has a history of lung disease
• Has a history of inflammatory bowel disease
• Has preexisting gastrointestinal (GI) or non-GI fistula
• Has malabsorption due to prior GI surgery or disease
• Has previously received treatment with a combination of pembrolizumab plus lenvatinib
• Has received prior treatment with belzutifan
• Has received prior radiotherapy within 2 weeks of start of study intervention
• Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention; killed vaccines are allowed
• Has received more than 4 previous systemic anticancer treatment regimens
• Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B
• Has had an allogenic tissue/solid organ transplant

• histologically or cytologically confirmed unresectable advanced or metastatic nccRCC, including but not limited to:
• Papillary RCC, any type
• Unclassified RCC
• Translocation RCC
• Chromophobe RCC
• Collecting duct RCC
• Medullary RCC
• Renal cell carcinoma with 80% or more sarcomatoid features on primary nephrectomy specimen or a biopsy
• Other nccRCC histologies
• Measurable disease as per RECIST 1.1. See Section 11 for the evaluation of measurable disease.
• Age ≥ 18 years
• ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A)
• Participants must undergo fresh tumor biopsy after registration but prior to the start of treatment unless medically unsafe or not feasible. If a fresh tumor biopsy is not medically safe or not feasible, confirmation of the availability of archival tumor tissue is required. For archival tissue, a recommended minimum of 20 unstained slides should be obtained.
• Normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• hemoglobin ≥9g/dL (transfusions allowed)
• total bilirubin ≤2.0 x institutional upper limit of normal with the following exception: patients with known Gilbert disease should have a serum bilirubin ≤ 3 x ULN
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal with the following exception: patients with known liver metastases should have AST and ALT ≤ 5 x ULN
• creatinine clearance ≥30 mL/min/1.73 m2 according to the Cockcroft-Gault equation.
• Normal coagulation INR ≤ 1.5
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 5 months after the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of cabozantinib, nivolumab or ipilimumab administration.
• Ability to understand and willingness to sign a written informed consent document
•Patients could be untreated or have received prior lines of therapies. Patients who receive prior therapy may receive only one VEGF based therapy. A combination therapy (e.g. lenvatinib+everolimus) is considered 1 line of therapy.
• Previous therapy with CD137 agonists and immune checkpoint inhibitors, including but not limited to inhibitors of the PD-1/PD-L1 and/or CTLA-4 axes. Previous treatment with IFNα or IL-2 is allowed if received > 4 weeks from enrollment.
• Treatment with small molecule tyrosine kinase inhibitors within 2 weeks of enrollment, or any other anticancer agent within 4 weeks of enrollment.
• Prior therapy with cabozantinib
• Patients receiving any other therapeutic investigational agents.
• Treatment with hydroxychloroquine within two weeks of treatment start.
• Radiotherapy for nccRCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
• Untreated brain metastases. Patients might be included if they underwent radiation therapy or surgery at least 4 weeks prior enrollment. Stability of the central nervous system disease should be confirmed by brain MRI or CT-scan or as determined by treating investigator. Patients should not be receiving prednisone dose >10 mg/d at C1D1.
• Other malignancy diagnosed within 2 years of first study treatment unless negligible risk of metastases or death (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma, or other malignancy not deemed to impact patients 5-year life expectancy).
• Significant cardiovascular disorders including:
• Significant cardiovascular disease including dyspnea of New York Heart Association (NYHA) class II or greater, myocardial infarction within the previous 3 months of first study treatment, unstable arrhythmias, unstable angina. Patients with known coronary artery disease or congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50%, must be on a stable and optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
• Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy is allowed.
• Personal history of hypertensive crisis or hypertensive encephalopathy within the previous 3 months of registration.
• Personal history of stroke or transient ischemic attack within 3 months of registration.
• Significant vascular disease, such as but not limited to aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis, within 6 months of registration.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG). Furthermore, subjects with a history of additional risk factors for torsades de pointes (eg, long QT syndrome) are also excluded.
• Known history of severe allergic reactions attributed to compounds of similar chemical or biologic composition human antibodies, or known hypersensitivity to any component of cabozantinib, nivolumab or ipilimumab products.
• Systemic immunosuppressive medications including but not limited to: Corticosteroids at a dose > 10mg equivalent prednisone daily, cyclosporin, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor (TNF) agents, hydroxychloroquine, within 2 weeks of first study dose.
• Patients who have received acute, low-dose systemic immunosuppressant medications may be enrolled.
• Patients with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled.
• The use of inhaled, topical, intraocular, or intraarticular corticosteroids or mineralocorticoids are allowed
• Prior allogenic stem cell or solid organ transplant.
• Personal history of autoimmune disease including: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on thyroid replacement hormone, or those with autoimmune dermatologic conditions not requiring the use of prednisone > 10 mg or equivalent are eligible.
• History of idiopathic pulmonary fibrosis, organized pneumonia, or evidence of active pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in the radiation field is permitted.
• History of following infectious diseases:
• Active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening).
• Active hepatitis C infection. Patients with positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
• Infection requiring therapeutic oral or IV anti-microbials within 2 weeks of first study treatment. Patients receiving routine antimicrobial prophylaxis for dental procedures are eligible.
• Known positive test for HIV.
• Administration of a live, attenuated vaccine within 3 weeks for first study treatment.
• Bleeding diathesis, or significant coagulopathy in the absence of therapeutic anticoagulation.
• Use of strong inhibitors and inducers of CYP3A4
• Significant bleeding, including but not limited to hematemesis, hematuria, hemoptysis of > 0.5 teaspoon (2.5 mL), within 3 months before registration.
• Invasion of major pulmonary blood vessels. A discussion with PI may be needed if invading lesions are suspected.
• Concomitant use of dipyramidole, ticlopidine, clopidogrel, cilostazol is excluded. Aspirin (≤ 325 mg per day) is allowed. Prophylactic anticoagulation with oral or parenteral anticoagulants for the patency of venous access devices or other indications is allowed. Therapeutic use of low-molecular weight heparin (such as enoxaparin) and subcutaneous or oral Factor Xa inhibitors are allowed. Use of warfarin is prohibited.
• Significant GI conditions at risk of perforation or bleeding, including but not limited to:
• Active GI obstruction or requirement of routine parenteral nutrition or tube feedings.
• Personal history of abdominal or tracheoesophageal fistula or GI perforation within 6 months of registration.
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
• Serious, non-healing or dehiscing wound or active ulcer.
• Major surgical procedure to include major dental, oral or maxillofacial procedures within 14 days of first study treatment.
• Proteinuria as demonstrated by > 1.5 gram of protein in a 24-hour urine collection. All patients with ≥ 2+ protein on urinalysis must undergo 24-hour urine collection for protein.
• Unable to swallow pills.
• Malabsorption syndrome.
• Inability to receive IV medications
• Pregnant or lactating women.

• Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite…." question that requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
• Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
• No use of androgens, progesterone analogs, or other appetite stimulants within the past month
• Patient should not have poorly controlled hypertension or congestive heart failure at registration
• Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
• Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
• Patient should not have had a previous blood clot at any time in the past
• No history of poorly controlled diabetes
• No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
• No history of hypersensitivity to olanzapine or megestrol acetate
• No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 14 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Estimated life expectancy of 3 months or longer
• Serum creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
• Fasting glucose > 1410 mg/dl
• Granulocytes > 1000/hpf
• No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
• In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• Patients who cannot swallow oral formulations of the agents
• Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate)

1. Hemodynamically stable, as determined by the trauma team 2. Age 8 through 18 years (inclusive) 3. Interpretable CT of the abdomen and pelvis that demonstrates at least one solid organ injury among the liver, spleen, pancreas, and kidneys 4. Plan for observation or admission to the hospital 5. Candidate for abdominal ultrasound based on body habitus, as determined by the investigator 6. Glasgow Coma Score of 15 7. Able to complete the study procedures within 48 hours of injury 1. Known cardiac abnormality 2. Pulmonary Hypertension 3. Known sensitivity to any Lumason components
•including sulfur hexafluoride, polyethylene glycol 4000, distearoylphosphatidylcholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na), or palmitic acid 4. Unable to be rolled onto side to allow lateral ultrasound windows if necessary 5. Unable to assent or consent 6. Pregnant 7. Lactating 8. CT images not available for transmission to central image repository

• Adults 18-55 years of age at the time of informed consent
• Diagnosis of classical phenylketonuria (PKU) due to PAH deficiency
• Four baseline plasma Phe values with a concentration of ≥ 600 μmol/L and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
• Participants must have uncontrolled classical PKU disease (despite Phe-restricted dietary management) in the judgment of the investigator and confirmed by the independent DMC at the end of the Screening period.
• Participant has the ability and willingness to maintain their baseline diet, for the duration of the trial, unless otherwise directed
• Subjects with PKU that is not due to PAH deficiency
• Presence of anti-AAVHSC15 neutralizing antibodies
• Participants who are well controlled on a Phe-restricted diet.
• Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
• Liver function tests > ULN
• International normalized ratio (INR) > 1.2
• Hematology values outside of the normal range
• Previously received gene therapy for the treatment of any condition.

• Histologically confirmed, non-muscle invasive urothelial carcinoma with carcinoma in situ (CIS) (with or without papillary disease)
• Predominant histologic component (>50 percent) must be urothelial (transitional cell) carcinoma
• Participants must have high-risk Bacillus Calmette-Guerin (BCG)
•unresponsive disease, defined as (where adequate BCG therapy is defined as one of the following: 5 of 6 doses of an initial induction course + at least 2 of 3 doses maintenance therapy or 5 of 6 doses of an initial induction course + at least 2 of 6 doses of a second induction course):
• Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy.
• Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy, or
• T1 high-grade disease at the first evaluation following an induction BCG course (at least 5 or 6 doses)
• Participant must be ineligible for or refusing a radical cystectomy
• All visible papillary Ta/T1 tumors must be completely resected within 60 days prior to enrollment.
• Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.
• Current or prior history of muscle-invasive urothelial carcinoma or metastatic disease.
• Nodal or metastatic disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months prior to study treatment
• Concomitant upper tract urothelial carcinoma as noted on CT or MRI urogram performed within 3 months prior to study treatment
• Prior or concomitant urothelial carcinoma of the prostatic urethra within 6 months prior to study treatment
• Participants with tumor-related hydronephrosis
• Participant has received other systemic anticancer therapy including chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, and/or investigational agent within 4 weeks or intravesical therapy within 6 weeks of first dose of study treatment
• Participant has had any prior radiation to the bladder for urothelial cancer

1. Radiographic evidence of renal cancer with IVC tumor thrombus 2. Tumor thrombus must be ≥ level II (As per Mayo classification, it would be ≥ level I [Refer to NEVES, R. and ZINCKE, H. (1987), Surgical Treatment of Renal Cancer with Vena Cava Extension. British Journal of Urology, 59: 390-395. doi:10.1111/j.1464-410X.1987.tb04832.x]) 3. Patient eligible for SABR to the IVC tumor thrombus as decided by the treating radiation oncologist 4. Patient eligible for IVC tumor thrombectomy as decided by the treating urologist 5. Any number of metastatic disease is allowed in the Pilot phase of the trial • For Phase II, metastatic patients will be allowed only if all sites of metastasis has been treated either surgically or radio-surgically (If limited sites of metastasis are present, all of which can be resected during the nephrectomy, then the patient can be eligible) 6. Age ≥ 18 years. 7. Performance status ECOG 0-2 8. Any serum Albumin is allowed, but ≥ 3.4 g/dL is strongly encouraged • Serum albumin <3.4 is a significant predictor of peri-operative mortality(12) 9. Any serum AST is allowed but serum AST ≤ 34 IU/L is strongly encouraged • Significant predictor of mortality in univariate but not multivariate analysis(12) 10. Women of childbearing potential and men must agree to use adequate contraception (hormonal such as birth control pills, patch or ring; Depo-Provera, Implanon or barrier method, such as condom or diaphragm used with a spermicide of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 90 days following completion of radiation therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 10.1 A female of childbearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). 11. Ability to understand and the willingness to sign a written informed consent. 12. Subjects must be able to undergo either MRI or CT. 1. Subjects who have had radiotherapy to a target within 3 cm of the IVC tumor thrombus. 2. Subjects may have received any other investigational agents or chemotherapy as long as they are eligible for SABR and surgery 3. Subjects with brain metastases should be excluded from this clinical trial unless all the metastasis are treated surgically or radio-surgically 4. Subjects with a history of pulmonary embolism is excluded 5. Subjects with a history of pulmonary hypertension is excluded 6. Subjects must not be pregnant due to the potential for congenital abnormalities. 7. Contraindication for contrast-enhanced MRI as defined by the standard operating procedures of the Department of Radiology at UT Southwestern. Briefly, these include medically unstable; cardiac pacemaker; intracranial clips, metal implants; metal in the eyes; pregnant or nursing; claustrophobia; and impairment of the renal function with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2. Patients with one or more of these contraindications but eligible to undergo contrast-enhanced CT can participate in this study and will not receive an MRI

• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting 2022): In stage 2 of the study, no tumor samples will be submitted for centralized clinical tumor profiling; instead, a tumor molecular profiling report from a College of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments (CLIA)-approved testing laboratory must be submitted for review by the Molecular Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was obtained at any point after initial tumor recurrence/progression and must be accompanied by a pathology report for the same tumor specimen; a molecular profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that molecular profiling reports are available from multiple timepoints, the most recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic deficits in patients with central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have radiographically measurable disease; measurable disease based on imaging obtained less than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
• Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive: for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells, etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols

• Patients with histologically confirmed solid tumor malignancies with residual tumors present that require standard of care chemotherapy for a minimum number of cycles. All anatomical sites and all tumor histologies are eligible including central nervous system tumors. Both newly diagnosed and/or newly relapsed patients are eligible.
• Patients ages 8
•25 years
• In the opinion of the investigator, patients must be thought to be able to lie still for imaging without sedation for 20
•30 minutes.
• Patients must have a performance status of > 50% (Lansky or Karnofsky).
• Patients of childbearing potential must have a negative urine or serum pregnancy test as per institution's standard of care within 7 days prior to [18F]FLT PET/CT imaging.
• Ability to understand and the willingness to sign a written informed consent/assent.
• Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals of similar chemical or biologic composition to [18F]FLT
• Newly diagnosed subjects who had prior chemotherapy or radiotherapy before enrollment in the study. Relapsed patients are eligible prior to starting their relapsed chemotherapy regimen if they meet the other eligibility criteria.
• Subjects for whom chemotherapy is not a standard of care primary therapy option.
• Patients who are pregnant or breast-feeding.
• Patients with no residual tumor (i.e. complete resection at diagnosis or relapse).

Key 1. Documented genetic ALK, ROS1, or NTRK1-3 alteration (point mutation, fusion, amplification) as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required. 2. Phase 1: Age <12 years; Phase 2: Age 12- 25 years 3. Prior cytotoxic chemotherapy is allowed. 4. Prior immunotherapy is allowed. 5. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1. 6. All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria at time of enrollment. 7. Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 14 days prior to enrollment. 8. Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least 50. 9. Life expectancy greater than or equal to 12 weeks. 10. Adequate hematologic, renal and hepatic function. Phase 2 1. Cohort Specific
• Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
• Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
• Cohort 3: subjects with tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease or not otherwise eligible for Cohort 1 or 2. 2. Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2): 1. Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only. 2. Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery. 3. Known active infections (bacterial, fungal, viral including HIV positivity). 4. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption. 5. Any of the following cardiac criteria:
• Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval 6. Peripheral neuropathy of CTCAE ≥grade 2. 7. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.

• STEP 1 REGISTRATION: If this will be the first patient from a registering site to receive a given RT modality (3DCRT vs. IMRT), the site must first submit pre-RT planning documents within 3 days of Step 1 registration and receive approval from Imaging and Radiation Oncology Core (IROC) before randomizing the patient to Step 2. If this will not be the first patient to receive a specific RT modality, the patient should be immediately randomized to Step 2 on the same day.
• STEP 2 RANDOMIZATION: If patient required review of pre-RT planning, randomization must occur within 14 days of initial registration.
• Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the bladder within 120 days prior to randomization and no intervening treatment between the histologic proof and randomization. Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible. Patients with lymph nodes >= 1.0 cm in shortest cross-sectional diameter on imaging (computed tomography [CT]/magnetic resonance imaging [MRI] of abdomen and pelvis) must have a biopsy of the enlarged lymph node showing no tumor involvement within 70 days prior to randomization. These patients may be suitable for neoadjuvant chemotherapy and radical cystectomy and are eligible for this trial if they seek out a bladder sparing treatment strategy, however patients who have received prior systemic chemotherapy for bladder cancer are not eligible for the trial.
• Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70 days prior to randomization. In a situation where a patient is referred from outside to the enrolling institution, patient must have a repeat office cystoscopy by the urologist who will be following the patient on the clinical trial to assess the adequacy of the prior TURBT. This cystoscopy can be performed in urologist office without general anesthesia. Patient may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection. Patient must not have T4b disease
• Patients must undergo radiological staging within 70 days prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Patients must not have evidence of T4bN1-3 disease. Eligibility is based on the local radiology report.
• Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meets criteria specified.
• Patient must be planning to receive one of the protocol specified chemotherapy regimens.
• All adverse events associated with any prior surgery and intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade =< 2 prior to randomization.
• Patients must be >= 18 years of age
• Patient may or may not be radical cystectomy candidates.
• Absolute neutrophil count (ANC) >=1,500/microliter (mcL) (within 28 days prior to randomization).
• Platelets >= 100,000/mcL (within 28 days prior to randomization).
• Hemoglobin >= 9 g/dL (within 28 days prior to randomization).
• Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 28 days prior to randomization).
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN (within 28 days prior to randomization).
• Patients must have adequate renal function as evidenced by calculated creatinine clearance >= 25 mL/min. The creatinine used to calculate the clearance result must have been obtained within 28 days prior to randomization.
• Patients must have Zubrod performance status =< 2.
• Patients must have a baseline electrocardiography (ECG) performed within 30 days prior to randomization.
• If patient has a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV), they must meet the following criteria within 28 days prior to randomization.
• Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
• Patients who are known to be positive for human immunodeficiency virus (HIV) are eligible only if they have all of the following:
• A stable regimen of highly active anti-retroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
• A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests within 28 days prior to randomization.
• Female patients of childbearing potential must have a serum pregnancy test prior to randomization. Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of protocol treatment, and for 5 months (150 days) after the last dose of all study drugs. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months.
• Patients must be offered the opportunity to participate in specimen banking for future studies.
• Patients who can complete Patient-Reported Outcome instruments in English or Spanish must agree to complete the EORTC QLQ-C30, the EORTC QLQ-BLM30, the EPIC Bowel Assessment, and the EQ-5D-5L per protocol schedule of assessment.
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
• Patients must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy.
• Patients must not have diffuse CIS based on cystoscopy and biopsy.
• Patient must not have received any systemic chemotherapy for their bladder cancer.
• Patient must not have had prior pelvic radiation.
• Patients must not have received prior treatment for muscle invasive bladder cancer including neoadjuvant chemotherapy for the current tumor.
• Patients must not have received any systemic therapy (including, but not limited to, interferon alfa-2b, high dose IL-2, pegylated interferon [PEG-IFN], anti-PD-1, anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical bacillus Calmette-Guerin (BCG), interferon, and intravesical chemotherapy are allowed.
• Patients must not have received any of the following prohibited therapies within 28 days prior to randomization or be planning to receive any of the following prohibited therapies during protocol treatment:
• Anti-cancer systemic chemotherapy or biological therapy not specified in the protocol.
• Immunotherapy not specified in this protocol.
• Systemic or intravesical use of any non-study anti-cancer agent (investigational or non-investigational).
• Investigational agents other than atezolizumab.
• Live vaccines: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed. Prior administration of intravesical BCG is allowed.
• Glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology. The use of physiologic doses of corticosteroids (defined as 10 mg prednisone) are acceptable, however site investigators should consult with the study chair for any dose higher than 10 mg prednisone. Dexamethasone 4 mg IV with chemotherapy to prevent nausea is allowed.
• RANKL infusion: Concurrent denosumab (which binds the cytokine RANKL) for any known indication is prohibited due to interaction with study medication.
• Patients must not have a major surgical procedure within 28 days prior to randomization. If patient had any surgical procedure then they should have recovered to full presurgical performance status and surgical adverse events should have resolved to grade =< 2. TURBT is not considered a major surgical procedure.
• Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization. Exceptions:
• Patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea).
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. Physiological doses equivalent of 10 mg prednisone daily are allowed. Short term steroids given as antiemetic therapy, e.g. 4 mg dexamethasone or equivalent once a week, is allowed.
• Patients must not have received a live, attenuated vaccine within 4 weeks prior to randomization or anticipate that such a live, attenuated vaccine will be required while on protocol treatment and up to 5 months after the last dose of protocol treatment.
• Inactivated influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior to randomization or while on protocol treatment and up to 5 months after the last dose of protocol treatment.
• Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Patients must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease).
• Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis.
• Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to randomization. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are not eligible. If patient develops urinary tract infection after TURBT they must have recovered from the infection prior to registration.
• Patients must not have active autoimmune disease that has required systemic treatment in past two 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. Autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, Graves' disease treated with methimazole or glomerulonephritis.
• Patient must not have a history of active tuberculosis.
• 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 two years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible.
• Patients must not be known to be allergic to Chinese hamster egg or ovary cell products and must not have any known major allergic reactions to any study drug.

1. Male or female adults aged 18 years or greater. There will be no upper age limit. 2. Presence of CKD stages 3b, 4 or non-dialysis stage 5, with an estimated glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 for a period of at least 3 months, as defined by the National Kidney Foundation and determined using the four-variable Modification of Diet for Renal Diseases Study formula. 3. Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based criteria 4. Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization. 5. Able to understand and sign informed consent after the nature of the study has been fully explained 1. Unable to understand or give informed consent. 2. Unwilling or unable to participate in the protocol or comply with any of its components 3. Receiving chronic dialysis 4. Kidney transplant recipient 5. Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than the upper limit of normal 6. Terminal chronic obstructive pulmonary disease or cancer 7. Presence of seizure disorder 8. Current use of class I anti-arrhythmic medications (such as 1C propafenone and flecanide), pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine, or methyldopa; tri-cyclic anti-depressants, neuroleptics, or anti-convulsants 9. Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort. 10. Use of medications known to cause QT prolongation on EKG 11. Ongoing use of antidepressant medications for depression treatment 12. Past treatment failure on bupropion 13. Initiation of depression-focused psychotherapy in the 3 months prior to study entry 14. Active alcohol or substance abuse or dependence that requires acute detoxification at study entry 15. Present or past psychosis or Bipolar I or II disorder 16. Dementia or a Mini-Mental State Examination score <23 17. Active suicidal intent 18. Pregnancy, lactation, or women of childbearing potential not willing to use adequate contraception

• Documented histologic or cytologic diagnosis of renal cell cancer (RCC). All subtypes of RCC are eligible including but not limited to clear cell, papillary, chromophobe, translocation, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Enrollment of non-clear cell patients will be limited to 20% of the total sample size (~ 42 patients). Once this goal is met, accrual of non-clear cell patients will be discontinued (a notice will be sent out 2 weeks in advance). Sarcomatoid and rhabdoid differentiation are allowed
• Presence of at least 1 metastatic bone lesion not treated with prior radiation is required.
• The presence of bone metastases can be detected by computed tomography (CT), magnetic resonance imaging (MRI), Tc-99m bone scan or positron emission tomography (PET) (fludeoxyglucose F-18 [FDG] or sodium fluoride [NaF]) imaging. Patients with non-measurable bone-only disease are allowed. Patients may have received prior radiation therapy for bone metastases or other external radiation >= 7 days prior to registration, as long as they still have at least 1 metastatic bone lesion not treated with radiation. Patients with visceral metastases are allowed, as long as they have at least one untreated bone metastases
• No prior treatment with cabozantinib
• No treatment with any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks or 5 half-lives (whichever is shorter) of registration or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of registration
• No prior hemibody external radiotherapy
• No prior therapy with radium-223 dichloride or systemic radiotherapy (such as samarium, strontium)
• No major surgery within 6 weeks of randomization. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Moh's or other topical skin surgery, Lasik eye surgery are not considered major surgery. Patients who have had a nephrectomy may be registered >= 3 weeks after surgery, providing there are no wound-healing complications. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
• Recovery to baseline or =< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy
• The use of osteoclast targeted therapy including either bisphosphonates or denosumab is mandated on this study except in patients with contraindications as determined by the treating investigator, including:
• Hypocalcemia
• Hypophosphatemia
• Renal impairment including those with a glomerular filtration rate (GFR) < 35 mL/min using the Cockcroft-Gault equation or acute renal impairment
• Hypersensitivity to drug formulation
• Dental condition or need for dental intervention that per the investigator would increase the risk of osteonecrosis of jaw (ONJ).
• Use of osteoclast targeted therapy or reason against use needs to be recorded in the electronic case report form (eCRF). Additionally, reason for discontinuation of osteoclast targeted therapy need to be appropriately documented in the eCRF
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
• Therefore, for women of childbearing potential only, a negative urine pregnancy test done =< 28 days prior to registration is required. A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Karnofsky performance status >= 60%
• No brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
• No imminent or established spinal cord compression based on clinical symptoms and/or imaging. In patients with untreated imminent or established spinal cord compression, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
• No imminent or impending pathologic fracture based on clinical symptoms and/or imaging. In patients with untreated imminent or impending pathologic fracture, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
• No significant, uncontrolled intercurrent or recent illness, including but not limited to the following conditions:
• Cardiovascular disorders: Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia; uncontrolled hypertension defined as sustained blood pressure > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment; stroke (including transient ischemic attack), myocardial infarction, or other ischemic event, within 6 months before randomization; thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization
• Gastrointestinal disorders: Disorders associated with a high risk of perforation or fistula formation: active inflammatory bowel disease, active diverticulitis, active cholecystitis, active symptomatic cholangitis or active appendicitis, active acute pancreatitis or active acute obstruction of the pancreatic or biliary duct, or active gastric outlet obstruction; abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 3 months before randomization. Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization
• No clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before randomization
• No lesions invading major pulmonary blood vessels
• No other clinically significant disorders:
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol [e.g. drug-drug interactions]) with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol [e.g. drug-drug interactions]), if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (with no medications prohibited by this protocol [e.g. drug-drug interactions])
• No serious non-healing wound or ulcer
• No malabsorption syndrome
• No uncompensated/symptomatic hypothyroidism
• No moderate to severe hepatic impairment (Child-Pugh B or C)
• No requirements for hemodialysis or peritoneal dialysis
• No history of solid organ transplantation
• No chronic concomitant treatment with strong CYP3A4 inducers or inhibitors. Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference. Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration
• No concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants include:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 9 g/dl (transfusions allowed)
• Calculated (calc.) creatinine clearance >= 30 mL/min using the Cockcroft-Gault equation
• Total bilirubin =< 1.5 x upper limit of normal (ULN), for patients with Gilberts disease =< 3.0 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
• Urine protein to creatinine (UPC) ratio =< 2 mg/mg OR 24-hr urine protein < 2 g

Key Inclusion Criteria Participants must meet all of the following criteria in order to be eligible to participate in the study:
• Male or female ≥1 year of age.
• Had an allogeneic hematopoietic cell transplant (HCT) performed ≥21 days and ≤1 year prior to randomization.
• Myeloid engraftment confirmed, defined as an absolute neutrophil count ≥500/mm³ for 3 consecutive laboratory values obtained on different days, and platelet count >10,000/mm³ at the time of randomization.
• Diagnosed with HC based on the following criteria (all 3 criteria must be met): 1. Clinical signs and/or symptoms of cystitis. 2. Grade ≥3 hematuria, defined as macroscopic hematuria with visible clots. 3. Viruria with ≥1 target virus (ie, BKV, JCV, AdV, CMV, EBV, and/or HHV-6).
• At least 1 identified, suitably matched posoleucel (ALVR105) cell line for infusion is available. Key Exclusion Criteria Participants who meet any of the following criteria will be excluded from participation in the study:
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
• Therapy with antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies ≤28 days before randomization.
• Evidence of active Grade >2 acute graft versus host disease (GVHD).
• Uncontrolled or progressive bacterial or fungal infections.
• Uncontrolled or progressive viral infections not targeted by posoleucel (ALVR105).
• Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder.
• Known or presumed pneumonia secondary to any organism that is not considered to be well-controlled by antimicrobial therapy.
• Pregnant or lactating or planning to become pregnant. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Inclusion Criteria
• Bladder cancer, confirmed pathologically on transurethral resection of bladder tumor (TURBT) or on bladder biopsy. Pure urothelial, variant urothelial, or any proportion of squamous cell carcinoma are permitted. Questions about eligibility may be resolved by consultation with UTSW pathology but formal pathologic review is not required.
• Bulky, clinically node positive disease (cN+) defined as: 1) a single pelvic lymph node of ≥ 1.5 cm largest diameter on CT or MRI; or 2) multiple pelvic lymph nodes ≥ 1 cm largest diameter on CT or MRI. Pathologic confirmation is not required. Imaging to establish eligibility must have been obtained no more than 60 days prior to trial enrollment. The scans must be personally reviewed by the enrolling clinician. For imaging studies obtained outside of UT Southwestern, imaging review of node status and sign off by the enrolling investigator is required. Review and sign off by a UTSW radiologist is optional in ambiguous or questionable cases, but is not mandatory.
• Age ≥ 18 years.
• ECOG performance status 0-1.
• Appropriate candidate for radical cystectomy, as determined by the treating urologist.
• Appropriate candidate for stereotactic ablative radiotherapy, as determined by the treating radiation oncologist.
• Patient is planned to initiate or is within 1-3 weeks of initiation of FDA-approved immune checkpoint inhibitor therapy based on ineligibility to receive platinum-based downstaging chemotherapy (DCT) (Cohort 1, as detailed below) or failure to achieve clinical complete response to platinum-based DCT (Cohort 2, as detailed below). Cohort 1 (chemotherapy-ineligible)
•either of:
• patient staged with bulky cN+ disease as defined above, medically ineligible to receive any platinum-based chemotherapy or, after appropriate and documented counseling, refusing to receive any-platinum-based chemotherapy; or
• patient staged with bulky cN+ disease as defined above, medically ineligible to receive cisplatin-based chemotherapy, with PD-L1 positive tumor (according to methodology described in the FDA approval label for the respective ICI agent) Cohort 2 (chemotherapy non-responding)
•any of:
• patient, initially staged with bulky cN+ disease as defined above, with radiologic progression after two cycles of platinum-based DCT (per RECIST 1.1 criteria: ≥20% increase in summed short-axis diameter of visible lesions with ≥ 5 mm absolute increase)
• patient, initially staged with bulky cN+ disease as defined above, failing to achieve radiologic complete response after three or four cycles of platinum-based DCT (failure of all enlarged lymph nodes to decrease to < 1 cm short-axis diameter)
• patient, initially staged with bulky cN+ disease as defined above, failing to achieve radiologic complete response after one or two cycles of platinum-based DCT which was discontinued due to patient intolerance
• patient, initially not staged with bulky cN+ disease as defined above, who progresses to cN+ disease as defined above after two or more of cycles of platinum-based DCT
• Permitted downstaging chemotherapy regimens are gemcitabine/cisplatin (gem/cis), gemcitabine/carboplatin (gem/carbo), and methotrexate/vinblastine/doxorubin/cisplatin (MVAC, in any dose variant).
• Permitted immune checkpoint inhibitor agents are those FDA-approved for platinum-ineligible (Cohort 1) or platinum-refractory (Cohort 2) bladder cancer: atezolizumab or pembrolizumab for Cohort 1; atezolizumab, avelumab, nivolumab, or pembrolizumab for Cohort 2. If additional immune checkpoint inhibitor (anti-PD1, anti-PD-L1, and/or anti-CTLA4) agents are approved for use in advanced urothelial carcinoma during the study, these agents will be permitted as well.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Medical or anatomic contraindication to any of the study treatment modalities (radical cystectomy, stereotactic ablative radiotherapy, immune checkpoint inhibitor therapy).
• Non-urothelial histology (other than pure squamous cell, which is permitted) including pure adenocarcinoma, pure small cell carcinoma, sarcoma, lymphoma, non-genitourinary primary (e.g. colorectal).
• Metastatic (cM1) disease, defined as 1) lymph nodes ≥ 1 cm above the aortic bifurcation (cM1a), or metastases to bone, brain, or any visceral site (cM1b). Patients with a single enlarged retroperitoneal lymph node will be eligible with an adequately performed lymph node biopsy showing no metastatic disease or with a PET scan showing absence of FDG avidity.
• Second primary malignancy, except: 1) non-metastatic (cM0) prostate cancer, 2) non-metastatic (cM0) endometrial cancer, 3) non-melanoma skin cancer, 4) cervical squamous cell carcinoma in situ, 4) any AJCC Stage I/II or organ-confined primary malignancy for which the patient has undergone curative treatment and has been without evidence of disease for three years.
• Prior pelvic radiation therapy.
• Autoimmune disease rendering the patient ineligible for ICI.
• Treatment with any immunosuppressive agent within 14 days of study entry, excluding topical or inhaled corticosteroids or adrenal-replacement steroids.
• End stage renal disease requiring dialysis.
• HIV infection, unless stable on HAART with CD4+ count > 400.
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab, avelumab, durvalumab, nivolumab, pembrolizumab, or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than atrial fibrillation / atrial flutter), or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

1. Male or female patients 18 to <70 years of age in the United States or 20 to <70 years of age in Japan at the time of obtaining informed consent. 2. Patients must be CMV seronegative pre-transplant and scheduled to receive or have received (within 7 days prior to first study drug administration) a first kidney transplant from a CMV seropositive donor. 3. Patients must be willing and able to give written informed consent for participation in the study. 4. Patients must be eligible to undergo kidney transplantation from a living or deceased donor, as per institutional standards. 5. Patients must agree with contraception by using appropriate contraceptive measures. 1. Patients who have received a previous solid organ transplantation or hematopoietic stem cell transplantation. 2. Patients who receive a multi-organ transplant. 3. Patients who have CMV disease or CMV viremia at Screening. 4. Patients who have a positive donor-specific antibody within 90 days prior to Randomization confirmed via medical records. 5. Patients whose body weight is more than 100 kg at Screening. 6. Patients who have received the following anti-CMV therapy within 7 days prior to Randomization and/or plan to receive the following anti-CMV therapy during the study: ・ Anti-CMV agents (eg, foscarnet, ganciclovir, valganciclovir, letermovir, high dose acyclovir, high dose valacyclovir, high dose famciclovir, or cidofovir). Note: The use of anti-CMV agents per local standard of care during the Rescue Phase of the study is permitted. Note: The use of anti-herpes simplex virus and anti-varicella zoster virus prophylaxis for at-risk patients is recommended (as long as the doses are below the one specified above). 7. Patients who have received the following therapy within 28 days prior to Randomization and/or plan to receive the following anti-CMV therapy during the study:
• CMV hyperimmune globulin (eg, CytoGam).
• Intravenous immunoglobulin.
• Plasmapheresis (receipt prior to first study drug administration is acceptable). 8. Patients with a history of a serious drug allergy to proteins, immunoglobulins, transfusions, or vaccines or any excipient of the NPC-21 formulation. 9. Patients with severe hepatic insufficiency at Screening (eg, Child-Pugh Class C). 10. Patients with active and untreated hepatitis B virus or hepatitis C virus, as documented as part of the pre-transplant screening. 11. Patients with known human immunodeficiency virus infection, based on medical records serology. 12. Patients with any uncontrolled infection at Randomization or a history of serious and uncontrolled infection within 6 months prior to Randomization. 13. Patients who are pregnant or lactating. 14. Patients with a history of malignancy within 5 years prior to Randomization other than curatively treated in situ cervical carcinoma, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma. 15. Patients with a history of alcohol or drug abuse or dependence within 1 year prior to Randomization that, in the opinion of the Investigator, would preclude study participation. 16. Patients who have previously participated in this study or any other study involving NPC-21. 17. Patients who have previously participated or are currently participating in any study involving the administration of a CMV vaccine or another CMV investigational agent. 18. Patients who have participated in another interventional clinical study and received another investigational product (ie, not approved by the Food and Drug Administration in the United States or the Ministry of Health, Labour and Welfare in Japan) within 90 days before Randomization. 19. Patients who are unable or unwilling, in the opinion of the Investigator, to comply with the protocol.

1. Male or female subjects ≥18 years of age at Screening. 2. Able and willing to comply with all study procedures. 3. Stable kidney function per Investigator assessment and no known episodes of AKI during the preceding 4 weeks. 4. Scheduled to undergo non-emergent coronary and/or valve surgery(ies) requiring cardiopulmonary bypass, including:
• CABG alone;
• Combined CABG surgery/repair of 1 or more cardiac valves;
• Cardiac valve(s) replacement or repair alone. 5. Females and males of childbearing potential must agree to use 2 forms of contraception, with at least 1 being a barrier method, or abstain from sexual activity for 30 days following study drug administration. 6. Male subjects must agree not to donate or sell sperm for 30 days following study drug administration. 1. Presence of AKI (KDIGO criteria) at the time of Screening. 2. Surgery to be performed without cardiopulmonary bypass. 3. Surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature <28°C (82.4°F). 4. eGFR ≤20 mL/min/1.73m2 or need for dialysis. 5. Surgery for aortic dissection or to correct a major congenital heart defect. 6. Administration of iodinated contrast media within 24 hours prior to cardiac surgery or evidence of contrast-induced nephropathy prior to cardiac surgery. 7. Cardiogenic shock or hemodynamic instability within the 24 hours prior to surgery and requirement for inotropes or vasopressors or other mechanical devices, such as intra-aortic balloon counter-pulsation. 8. Requirement for any of the following within 7 days prior to cardiac surgery:
• Defibrillator or permanent pacemaker;
• Mechanical ventilation;
• Intra-aortic balloon counter-pulsation;
• Left ventricular assist device;
• Other forms of mechanical circulatory support. 9. Known history of cancer within the past 2 years, except for carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin. 10. Known or suspected sepsis at time of Screening or confirmed or treated endocarditis within 30 days prior to cardiac surgery. 11. Other current active infection requiring systemic antibiotic treatment. 12. Inadequate hepatic function, defined as total bilirubin or alanine aminotransferase or aspartate aminotransferase >2X the upper limit of normal at time of Screening or Child Pugh Class C liver disease or higher. 13. Any congenital coagulation disorder. 14. Asplenia (anatomic or functional). 15. History of photosensitivity or active skin disease that, in the opinion of the Investigator, could be worsened by RBT-1. 16. Known hypersensitivity or previous anaphylaxis to SnPP or any tin-based product. 17. Serum ferritin >500 ng/mL or those who have received IV iron within 28 days of Screening. 18. Pregnancy or lactation. 19. Treatment with an investigational drug or participation in an interventional study within 30 days prior to administration of study drug. 20. In the opinion of the Investigator, any disease processes or confounding variables that would inappropriately alter the outcome of the study. 21. Inability to comply with the requirements of the study protocol.

• Ability to understand and the willingness to sign a written informed consent that includes study interventions (PET/CT and, if cohort 2, mandatory biopsy).
• Ability to lie still for a 30- to 60-minute PET/CT scan.
• One of the following: 1. Cohort 1. Patients with suspected RCC planned for surgery. 2. Cohort 2. Patients with metastatic ccRCC or VHL syndrome and RCC. Biopsy is required (planned resection for treatment reasons of a metastatic site is acceptable in lieu of the biopsy). 3. Cohort 3. Patients with VHL syndrome with RCC, CNS hemangioblastoma, and/or pancreatic neuroendocrine tumor(s) planning to start belzutifan.
• Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of [18F]PT2385 administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or celibate by choice) who meets the following criteria: 1. Has not undergone a hysterectomy or bilateral oophorectomy; or 2. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Claustrophobia or other contraindications to PET/CT.
• Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed (>200 kilograms or 440 pounds).
• For cohort 2 patients, lack of suitable sites for mandatory biopsy. For example, patients with metastatic disease restricted to the lungs that would require percutaneous biopsies with associated risk of bleeding and pneumothorax will be excluded.