• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment

Inclusion Criteria-Part A: Subject must meet all of the following applicable inclusion criteria to participate in this study:
• Patients must have histologically confirmed advanced RCC (any histology). Collecting duct tumors and tumors originating from the renal pelvis or upper urinary tract are considered of urothelial origin and are excluded from this protocol.
• Patients must have at least one measurable site of disease, per RECIST 1.1, that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Archival tissue of a metastatic lesion obtained within 1 year prior to study registration (within 4 weeks preferred) and tumor tissue from nephrectomy is required if available. In addition to archival tissue of a metastatic lesion and nephrectomy, patients must have at least one site of disease (not including bone metastases) accessible for biopsy. If biopsy/resection of a new lesion or primary tumor and slow freezing of fresh tissue for single cell RNAseq study (as specified in the CLM) is not feasible, the subject is not eligible for the study. All biopsies must be core needle or excisional. Fine needle aspirate is not acceptable. NOTE: The tissue collected from a surgical resection or multiple core biopsies of either a metastatic lesion or primary tumor for the slow freezing of fresh tissue after the patient has signed consent for the study could also be used for collecting the FFPE specimens.
• ECOG performance status 0-2.
• Age ≥ 18 years.
• Have signed the current approved informed consent form.
• Patients must have adequate organ function within 14 days prior to study entry as evidenced by screening laboratory values that must meet the following criteria:
• Hematological:
• White blood cell (WBC) ≥ 2000/µL
• Absolute Neutrophil Count (ANC) ≥ 1500/μL
• Platelets (Plt) ≥ 100 x103/μL
• Hemoglobin (Hgb) > 9.0 g/dL (with or without transfusion)
• Renal:
• Serum Creatinine ≤ 1.5 x ULN; if creatinine > 1.5, subject must demonstrate CrCl as outlined below.
• Calculated creatinine clearance ≥ 40 mL/min using Cockcroft-Gault formula
• Hepatic:
• Bilirubin ≤ 1.5× upper limit of normal (ULN); Except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL
• Aspartate aminotransferase (AST) ≤ 3 × ULN
• Alanine aminotransferase (ALT) ≤ 3 × ULN
• Patients should not have received prior systemic therapy for metastatic RCC. Prior radiotherapy must have been completed at least 2 weeks prior to the administration of study drug. Patients must be 2 weeks from prior major surgery and 1 week from pre-treatment biopsy. Prior systemic adjuvant therapy (excluding with PD1 or CTLA4 pathway blockers) is allowed if treatment completed > 12 months previously.
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of study drug. NOTE: Contraception is not required for male participants.
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) during screening for registration purposes. This pregnancy test should be repeated within 24 hours prior to the start of nivolumab. NOTE: "Women of childbearing potential" 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.
• Women must not be breastfeeding.
• Be willing and able to comply with this protocol.
• Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for 2 weeks of more after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
• Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected without recurrence or treated with SRS without progression x 4 weeks.
• Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
• Active infection requiring systemic therapy
• Has any other medical or personal condition that, in the opinion of the site investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's successful completion of the clinical trial
• Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Allergies and Adverse Drug Reaction
• History of allergy to study drug components
• History of severe hypersensitivity reaction to any monoclonal antibody
• Known additional malignancies within the past 3 years (excluding basal of squamous cell skin cancers, CIS or localized prostate cancer that has been treated or is being observed) Inclusion/Exclusion Criteria- Part B
• Must meet eligibility criteria for initiation of Part A with the exception of being allowed to have prior nivolumab in Part A of this protocol
• Must have evidence of either RECIST 1.1 defined Disease Progression or Stable Disease 1 year after initiating nivolumab therapy
• Tumor biopsy prior to combination treatment is mandatory. If a biopsy/resection of a new lesion or primary tumor and slow freezing of fresh tissue for single cell RNAseq study (as specified in the CLM) is not feasible, the subject is not eligible for the study. All biopsies must be core needle or excisional. Fine needle aspirate is not acceptable.
• Must not have had a Grade ≥ 3 irAE on nivolumab monotherapy
• Must not have untreated brain metastases
• Must not have had major surgery or radiation therapy within 14 days of starting study treatment
• Must not have active autoimmune disease
• Must not have a concurrent medical condition requiring use of systemic corticosteroids with prednisone >10 mg per day
• Must not have had prior systemic therapy for Stage IV RCC (except for nivolumab as part of part A of this protocol)
• Prior solid organ or stem cell transplant

Key
• Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) metastatic cancer of the following histologies: melanoma (MEL), Merkel cell carcinoma (MCC), triple-negative breast cancer (TNBC), renal cell carcinoma (RCC), colorectal cancer, head and neck squamous cell carcinoma (HNSCC), or sarcoma.
• Life expectancy > 12 weeks as determined by the Investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Measurable disease per RECIST 1.1.
• Patients enrolled in Cohorts 1-10, Cohort A, Cohort B and Phase 2 Doublet must be refractory to all therapies known to confer clinical benefit to their disease.
• Fresh tumor tissue available for cellular characterization and programmed cell death protein 1 (PD-L1) status.
• Injected lesions (up to two) must be between 20 mm and 90 mm in diameter for IT injection; lesions must be accessible for baseline and on-treatment biopsies. Any liver lesion targeted for injection must not exceed 50 mm at the time of injection.
• Demonstrated adequate organ function within 14 days of Cycle 1 Day 1 (C1D1). Key
• Use of an investigational agent or an investigational device within 21 days before administration of first dose of study drug(s).
• Patients treated with prior interleukin-2 (IL-2).
• Patients who have been previously treated with a toll-like receptor (TLR) agonist (excluding topical agents) and patients who have received experimental cancer vaccines.
• Patients who have received systemic interferon (IFN)α within the previous 6 months prior to enrollment to the study.
• Other active malignancy, except non-melanomic skin cancer
• Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
• Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients must have recovered from all radiation-related toxicities, not required corticosteroids and have not had radiation pneumonitis.
• Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening. History of unstable or deteriorating cardiac disease within the previous 6 months prior to screening including but not limited to the following:
• Unstable angina or myocardial infarction.
• Congestive heart failure (NYHA Class III or IV).
• Uncontrolled clinically significant arrhythmias.
• Patients with a history of any retinal disorders (e.g., retinal detachment, diabetic retinopathy, retinal hemorrhage, macular degeneration).
• Uveal melanoma will be excluded
• Patients with tumor that invade the superior vena cava or other major blood vessels. Additional general and tumor specific inclusion and exclusion criteria will apply.

• Provide written informed consent
• Histologically confirmed cancers for which no curative therapy exists
• Documented HER2 or EGFR exon 18 mutation
• Participants must agree and commit to use appropriate methods of contraception as outlined in the protocol
• At least one measurable lesion, defined by RECIST v1.1
• Participants harboring ineligible somatic HER2 mutations
• Prior treatment with any HER2-directed tyrosine kinase inhibitor (e.g., lapatinib, afatinib, dacomitinib, neratinib) is excluded with the following exception: patients with EGFR exon 18 mutated NSCLC who may have received afatinib, osimertinib, or other pan HER or EGFR TKIs remain eligible
• Participants who are receiving any other anticancer agents
• Symptomatic or unstable brain metastases
• Women who are pregnant or breast-feeding There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

• Diagnosis of overactive bladder with urgency urinary incontinence or mixed incontinence (urge and stress) with predominate urge, as confirmed by the MESA questionnaire;
• Women and men ≥ 18 years of age;
• Women of child-bearing age willing to practice birth control;
• At least 4 incontinent episodes associated with urgency on a 3-day voiding diary;
• At least 10 voids per day;
• Average urgency score of at least 2 as measured with IUSS on a 3-day voiding diary;
• Self-reported bladder symptoms present > 6 months;
• Documented failure of an adequate trial of first and second line therapy;
• Off all antimuscarinics and beta-3 adrenergic agonists for at least 2 weeks prior to enrollment;
• If on Tricyclic antidepressants, dosage must be stabilized for at least 3 months;
• Have no active urethral obstruction/stricture, bladder calculi or bladder tumor based on medical history;
• Normal upper urinary tract function based on medical history;
• Based on the medical opinion of the Investigator, there is no evidence of anatomic abnormalities that could jeopardize the placement of the device or pose a hazard to the subject;
• Based on the medical opinion of the Investigator, subject is willing and able to operate the patient programmer, recharging equipment, diary and has the ability to undergo study assessments and provide accurate responses;
• Based on the medical opinion of the Investigator, subject is a good surgical subject for the implant procedure;
• Capable of giving informed consent;
• Capable and willing to follow all study related procedures.
• An active implantable electronic device regardless of whether stimulation is ON or OFF;
• Pregnant as confirmed by a urine pregnancy test or plan to become pregnant during the following 12 months period;
• Primary complaint of stress urinary incontinence;
• Less than 1 year post-partum and/or are breast-feeding;
• Neurogenic bladder (i.e. Multiple sclerosis, Parkinson's, Spinal Cord Injury);
• Patients with spinal hardware that would limit access to the sacrum;
• Botox use in bladder or pelvic floor muscles in the past nine months;
• Have a post-void residual urine volume >150 cc at baseline;
• Current urinary tract infection (UTI);
• Previous treatment with sacral neuromodulation;
• Previous treatment with percutaneous tibial nerve stimulation, pelvic floor muscle stimulation, or biofeedback within the past 60 days;
• Conditions requiring Magnetic Resonance Imaging (MRI) evaluation or diathermy procedures;
• Inability to operate the CAN-Stim System or InterStim System;
• Diabetes with peripheral nerve compromise or severe uncontrolled diabetes (HbA1C 8.5 or greater);
• History of coagulopathy or bleeding disorder;
• History of pelvic pain as primary diagnosis (VAS score of > 4) at baseline;
• Anatomical restrictions such that device placement is not possible;
• Are currently participating or have participated within the past 30 days in any clinical investigation involving or impacting urinary or renal function;
• Have a life expectancy of less than 1 year;
• Cannot independently comprehend and complete the questionnaires and diaries;
• Deemed unsuitable for enrollment by the investigator based on history or physical examination (including bleeding disorders or anticoagulant medications, and peripheral neuropathy);
• Dependent on wearable, transcutaneous, or other therapeutic medical device (examples: glucose monitor, TENS) for treatment of a disease or disorder.

• Adult female patient 50 to 75 years of age who has primary and moderate-to-severe symptoms of SUI for at least 6 months, as confirmed by patient medical history and clinical symptoms, including a focused incontinence evaluation.
• Must be willing and able to comply with the study procedures, be mentally competent and able to understand all study requirements, and must agree to read and sign the informed consent form prior to any study-related procedures.
• Must have completed 100% of the screening 3-day diary evening reports.
• Patient has symptoms of only urge incontinence as confirmed by basic evaluation of etiology from a patient medical history, including a focused incontinence history.
• Patient has symptoms of mixed urinary incontinence where urge incontinence is the predominant factor.
• Patient has had stress urinary incontinence symptoms less than 6 months prior to signing the informed consent.
• Patient has not previously attempted conservative treatment prior to signing the informed consent. (Examples of conservative treatment include behavior modifications, bladder exercises, biofeedback, pelvic floor muscle therapy, etc.)
• Patient BMI ≥ 35.
• Patient routinely has more than 2 episodes of awakening to void during normal sleeping hours.
• If taking a medication known to affect lower urinary tract function, including but not limited to, anticholinergics, beta 3 adrenergic receptor agonists, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants, diuretics, or alpha-adrenergic blockers, patient cannot be maintained on a stable dose and/or frequency of medication (including diuretics), cannot be maintained on a stable dose and/or frequency for at least 2 weeks prior to screening or is likely to change during the course of the study.
• History of cancer in pelvic organs, ureters, or kidneys.
• Patient is pregnant, lactating, or plans to become pregnant during the course of the study.

• 18-80 years old
• Severe renal impairment (CrCl < 30 mL/min)
• Undergoing non-emergent surgery that requires neuromuscular blockade
• Planned extubation in the operating room immediately after surgery
• American Society of Anesthesiologists (ASA) physical status classification 3 to 4
• Willing and able to consent in English or Spanish
• No personal history of neuromuscular disease
• Age less than 18 or older than 80
• Patient does not speak English or Spanish
• Planned postoperative intubation/ventilation
• Allergy to sugammadex, neostigmine, glycopyrrolate, cisatracurium, or rocuronium
• Family or personal history of malignant hyperthermia
• Patient refusal
• Pregnant or nursing women
• "Stat" (emergent) cases
• Pre-existing muscle weakness of any etiology
• Patients on toremifene (a selective estrogen receptor modulator)
• Women on oral contraceptives who do not wish to use a non-hormonal method of contraception for 7 days following surgery

1. Signed informed consent and mental capability to understand the informed consent 2. Male or female patients > 18 years of age 3. Histologically or cytologically documented locally advanced or metastatic solid tumor malignancies refractory to or otherwise ineligible for treatment with standard-of-care agents/regimens, including but not limited to:
• Malignant melanoma
• Hormone receptor negative breast cancer
• Gastro-esophageal cancer
• Non-small cell lung cancer
• Head and neck cancer
• Hepatoma
• Renal cell carcinoma 4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 5. Evaluable or measurable disease as follows:
• A minimum of 3 RECIST-evaluable lesions: one that is suitable for injection and biopsied; one non-injected that will be biopsied for abscopal effect; and one measurable lesion that will be followed for response only.
• Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous injection only, including those lesions that are visible, palpable, or detectable by standard radiographic or ultrasound methods. Neither surgical procedures nor endoscopically-guided injections including those to endobronchial, endoluminal, or endosinusial spaces shall be allowed. While no anatomic locations are required or disallowed, lesions selected for intratumoral injection must, in the opinion of the investigator:
• Not be immediately adjacent to blood vasculature or other physiologic landmarks in such a way that will accrue undue safety risk to the patient
• Have longest diameter ≥ 10 mm and ≤ 50 mm
• Be fully efficacy evaluable per RECIST v1.1 criteria 6. Life expectancy > 3 months (Phase I) and > 6 months (Phase IIA) 7. ECG without evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the investigator 8. Acceptable organ and marrow function as defined below:
• Absolute neutrophil count > 1,500 cells/μL
• Platelets > 50,000 cells/μL
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤ 2.5 times ULN. If liver metastases are present, AST/ALT < 5 times ULN
• Serum creatinine < 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula
• Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 times ULN 9. Women of child-bearing potential (defined as a female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months with an appropriate clinical profile at the appropriate age, e.g., greater than 45 years) must have a negative serum pregnancy test prior to first dose of study drug 10. Male and female patients with reproductive potential must agree to use two forms of highly effective contraception throughout the study 11. Phase I combination only: Demonstrated RECIST stable disease through ≥ 4 consecutive cycles of an approved PD-1 or PD-L1 targeted ICI with no Grade ≥ 3 CTCAE events considered by the investigator to be drug-related. 1. Anti-cancer therapy within 4 weeks or < 5 half-lives of the first dose of study drug. 2. Failure to recover to Grade 1 or less from clinically significant AEs due to prior anti-cancer therapy. 3. Known untreated brain metastases or treated brain metastases that have not been stable (scan showing no worsening of central nervous system (CNS) lesion[s] and no requirement of corticosteroids) ≥ 4 weeks prior to study enrollment 4. Baseline prolongation of QT/QTc interval (QTc interval > 470) 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 opinion of the investigator would limit compliance with study requirements 6. Women who are pregnant or breastfeeding 7. Phase I combination only: Prior tumor progression through PD-1 or PD-L1 targeted ICI therapy.

Inclusion criteria
• Dry weight ≥ 7 kg during screening.
• Diagnosed with CKD and SHPT undergoing hemodialysis at the time of screening.
• Diagnosis of SHPT with the mean of the 2 consecutive central laboratory iPTH values ≥ 400 pg/mL (42 pmol/L) during screening, on separate days and within 2 weeks of enrolment.
• Serum cCa value ≥ 9.0 mg/dL (2.25 mmol/L) for subjects ≥ 2 years of age and older and serum cCa value ≥ 9.6 mg/dL (2.4 mmol/L) for subjects 28 days to < 2 years of age obtained from the central laboratory during screening.
• Dialysate Ca level ≥ 2.5 mEq/L during screening.
• SHPT not due to vitamin D deficiency, per investigator assessment. Exclusion
• Anticipated or scheduled parathyroidectomy or kidney transplant during the study period.
• Subject has received a parathyroidectomy within 6 months prior to randomization.
• Receipt of cinacalcet therapy within 30 days prior to screening assessments and through randomization.
• Receipt of etelcalcetide within 6 months prior to screening assessments and through randomization.

Patients who meet all of the following inclusion criteria will be eligible to participate in the study: 1. Male or female patients 18 years of age or older. 2. Patients must be eligible to undergo kidney transplantation from a living donor as per institutional standards. 3. For Groups 1 and 2 only: Patients must be CMV immunoglobulin G (IgG) seronegative (-) and receiving kidney for transplantation from donors who are CMV IgG seropositive (+). 4. For Group 3 only: Patients must be CMV immunoglobulin G (IgG) seropositive (+) and receiving kidney for transplantation from donors who are either CMV IgG seronegative (-) or seropositive (+). 5. Patients who would comply with the requirements of this protocol (e.g., return for follow up visits), as judged by the investigator. Patients who meet any of the following criteria will be excluded from the study: 1. Patients planning to undergo multi-organ transplantation. 2. Patients participating in another interventional clinical study. 3. Previous vaccination with an investigational CMV vaccine. 4. Any confirmed or suspected immunodeficiency disorder (based on medical history and physical examination) that could interfere with the immune response or that presents a risk for the patient to receive a vaccine candidate in development. 5. Treatment with any chronic immunosuppressive medication or other immuno modifying drugs within 6 months prior to study entry. However, inhaled and topical steroids and low-dose oral corticosteroids (<10 milligrams a day of prednisone or equivalent) are allowed. 6. Prior history of CMV disease or CMV infection requiring anti-viral therapy 7. Patients with a rash, dermatological condition, or tattoo in the area of the injection site(s) that could interfere with administration site reaction rating. (Note: The injection site(s) can be the non-dominant arm [most preferred injection site], dominant arm, or either thigh [least preferred injection site], as judged by the investigator). 8. It is anticipated that the patient will be unavailable to complete the study follow-up.

• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• Histologically confirmed locally advanced or metastatic clear cell renal cell carcinoma that has progressed during or after two prior therapeutic regimens which must include vascular endothelial growth factor (VEGF)-targeted therapy and checkpoint inhibitor therapy or that has otherwise failed such therapies, is measurable disease per RECIST 1.1 criteria, is biopsy accessible
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Estimated life expectancy of longer than 3 months
• Adequate organ function at screening
• History of untreated brain metastasis or leptomeningeal disease or spinal cord compression
• Failure to recover from reversible effects of prior anticancer therapy
• Has received systemic therapy or radiation therapy within 2 weeks prior to screen
• History of solid organ or stem cell transplantation
• Current use of anti-VEGF or mammalian target of rapamycin (mTOR) agents, or chronic immunosuppressive therapy
• Any prior use of hypoxia inducible factor 2 (HIF2) inhibitors
• Current use of immune checkpoint inhibitors
• Use of an investigational agent or device within 2 weeks prior to dosing, or current participation in an investigational study
• Known HIV, hepatitis B or hepatitis C
• History of other clinically meaningful disease
• Major surgery within 4 weeks of Screening
• Active malignancy requiring therapy other than ccRCC within 3 years of study entry

• Has a histologically confirmed diagnosis of locally advanced/metastatic RCC with clear cell component
• Has measurable disease per RECIST 1.1 as assessed by BICR
• Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Has experienced disease progression on or after systemic treatment with an anti-programmed cell death 1 (PD-1)/Ligand 1 (L1) therapy for locally advanced or metastatic RCC. The anti-PD-1/L1 therapy may be monotherapy or in combination with other agent(s) such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or vascular endothelial growth factor (VEGF) targeted- tyrosine kinase inhibitor (TKI). The immediately preceding line of treatment has to have been an anti-PD-1/L1 therapy
• Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
• Has received only 1 prior anti-PD-1/L1 therapy for locally advanced or metastatic RCC
• Has recovered from all AEs due to previous therapies to ≤Grade 1 or baseline, with the exception of ≤Grade 2 neuropathy or endocrine-related AEs ≤Grade 2 requiring treatment or hormone replacement
• Has a Karnofsky performance status (KPS) score of at least 70% assessed within 10 days prior to the first dose of study intervention
• A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of study intervention
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study intervention
• Has hypoxia (a pulse oximeter reading <92% at rest), requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction ≤6 months from Day 1 of study drug administration or New York Heart Association Class III or IV congestive heart failure
• Has moderate to severe hepatic impairment (Child-Pugh B or C)
• Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention
• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
• Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
• Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan) formulations
• Has received prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor
• Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) ≤2 weeks before randomization
• Has received any type of systemic anticancer antibody (including investigational antibody) ≤4 weeks before randomization
• Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
• Has had major surgery ≤3 weeks prior to first dose of study intervention
• Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
• Is currently participating in a study of an investigational agent or is currently using an investigational device
• Has an active infection requiring systemic therapy
• Has active tuberculosis (TB)
• Has a diagnosis of immunodeficiency
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not the best interest of the participant to participate, in the opinion of the treating investigator

• Patients who had a kidney transplant performed greater than or equal to 28 days prior to enrollment
• At least 1 identified, suitably matched Posoleucel (Viralym-M) cell line for infusion is available. (If a matching Posoleucel (Viralym-M) line is not available, the following patient data will be collected: demographic data and human leukocyte antigen [HLA] type.)
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A female patient is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
• She is a woman of non-childbearing potential (WONCBP) as defined in the protocol
• She is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as described in the protocol during the study treatment period and for at least 90 days after the last dose of study treatment. The Investigator should evaluate the potential for contraceptive method failure.
• Undergone allogeneic hematopoietic cell transplantation
• Evidence or history of graft versus host disease (GVHD) or cytokine release syndrome (CRS).
• Uncontrolled or progressive bacterial or fungal infections
• Known or presumed pneumonia
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
• Pregnant or lactating or planning to become pregnant.
• Weight <40 kg.
• Patients who received, or planned to receive abatacept, belatacept, sirolimus or everolimus within 3 months of screening

• Be male at any age.
• Be scheduled to undergo surgery, chemotherapy, drug treatment and/or radiation for the treatment or prevention of a medical condition or malignancy with risk of causing permanent and complete loss of subsequent testicular function.
• Or, have a medical condition or malignancy that requires removal of all or part of one or both testicles.
• Have newly diagnosed or recurrent disease. Those who were not enrolled at the time of initial diagnosis (i.e., patients with recurrent disease) are eligible if they have not previously received therapy that is viewed as likely to result in complete and permanent loss of testicular function.
• Have two testicles if undergoing elective removal of all or part of a testicle for fertility preservation only. Note: removal of both testicles will limit fertility preservation options.
• Sign an approved informed consent and authorization permitting the release of personal health information. The patient and/or the patient's legally authorized guardian must acknowledge in writing that consent for specimen collection has been obtained, in accordance with institutional policies approved by the U.S. Department of Health and
• Consent for serum screening tests for infectious diseases [HIV-1, HIV-2, Hepatitis B, Hepatitis C], to be performed at the time of testicular tissue harvesting.
• Undergo a full history and physical examination and obtain standard pre-operative clearance (based on the most recent ACC/AHA Guideline for Perioperative Cardiovascular Evaluation for Noncardiac Surgery) as determined by their primary surgeon.
• Participating in long term follow-up is a requirement of the protocol.
• Diagnosed with psychological, psychiatric, or other conditions which prevent giving fully informed consent.
• Diagnosed with an underlying medical condition that significantly increases their risk of complications from anesthesia and surgery.

• Has histologically confirmed diagnosis of RCC with clear cell component
• Has received no prior systemic therapy for advanced ccRCC
• Male participants are abstinent from heterosexual intercourse or agree to use contraception during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib
• Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) or use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after pembrolizumab or pembrolizumab/quavonlimab or for at least 30 days after last dose of lenvatinib or belzutifan, whichever occurs last
• Has adequately controlled blood pressure with or without antihypertensive medications
• Has adequate organ function
• Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks prior to randomization/allocation
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has had major surgery, other than nephrectomy within 4 weeks prior to randomization
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has received prior radiotherapy within 2 weeks prior to first dose of study intervention
• Has hypoxia or requires intermittent supplemental oxygen or requires chronic supplemental oxygen
• Has clinically significant cardiac disease within 12 months from first dose of study intervention
• Has a history of interstitial lung disease
• Has symptomatic pleural effusion; a participant who is clinically stable following treatment of this condition is eligible
• Has preexisting gastrointestinal or non-gastrointestinal fistula
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of noninfectious pneumonitis that required steroids or has current pneumonitis
• 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 radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel
• Has clinically significant history of bleeding within 3 months prior to randomization
• Has had an allogenic tissue/solid organ transplant

• Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis
• Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and lymphoma) that meets at least one of the following criteria:
• Refractory, defined as tumor progression after initiation of standard first line therapy without having achieved a prior partial or complete remission OR Biopsy proven residual disease at the completion of planned standard initial front-line therapy.
• Recurrent, defined as tumor progression after achieving a prior partial or complete remission
• Newly diagnosed high risk disease, defined as having an expected event free survival of < 50% at 2 years.
• Lacks definitive diagnosis or classical genomic findings after histologic review and standard molecular testing (rare tumor group).
• Examples include (eligibility not limited to these examples):
• Histology typically associated with a fusion in which fusion is not detected.
• Ewing-like sarcoma
• Undifferentiated sarcoma
• Inflammatory myofibroblastic tumor without ALK fusion
• Infantile fibrosarcoma without NTRK fusion
• Specimen Samples
• Sufficient tumor specimen available to meet the minimum requirements for profiling from diagnosis or progression / recurrence --- OR
• Surgery / biopsy planned as part of clinical care that is anticipated to yield sufficient material to meet the minimum requirements for profiling; OR
• Patient has already had molecular profiling and patient has not yet started matched targeted therapy based on the report .
• No Therapy Planned -- Patients who have declined further anticancer therapy will be excluded.
• Performance Status -- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will be excluded.
• Life Expectancy -- Patients with anticipated life expectancy < 3 months will be excluded.

Key 1. The patient or parent/legal guardian (as appropriate) is willing and able to provide signed informed consent, and where required, the patient is willing to provide assent, prior to any screening procedures. 2. The patient has biopsy-proven primary focal segmental glomerulosclerosis (FSGS) or documentation of a genetic mutation in a podocyte protein associated with FSGS. 3. Sites within the US: The patient is male or female aged 8 to 75 years, inclusive. Sites outside the US: The patient is male or female aged 18 to 75 years, inclusive. 4. The patient has a urine protein/creatinine (Up/C) ≥1.5 g/g at screening. 5. The patient has an eGFR ≥30 mL/min/1.73 m2 at screening. 6. Women of childbearing potential (WOCBP) must agree to the simultaneous use of 2 medically accepted methods of contraception from Day 1/Randomization until 90 days after the last dose of study medication. 7. Males must be surgically sterile (more than 3 months post-vasectomy) or must agree to the use of medically accepted methods of contraception that are considered highly reliable from Day 1/Randomization until 90 days after the last dose of study medication. Key 1. The patient has FSGS secondary to another condition. 2. The patient has positive serological tests of primary or secondary glomerular injury not consistent with a diagnosis of primary or genetic FSGS. 3. The patient has a history of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus. 4. The patient has undergone any organ transplantation, with the exception of corneal transplants, or has received certain immunosuppressive medications. 5. The patient has a documented history of heart failure, coronary artery disease or cerebrovascular disease. 6. The patient has significant liver disease. 7. The patient is positive at screening for the human immunodeficiency virus (HIV) or markers indicating acute or chronic hepatitis B infection or hepatitis C infection. 8. The patient has a history of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years. 9. The patient has disqualifying laboratory abnormalities during a screening. 10. The patient is >18 years of age with a body mass index (BMI) >40, or is ≤18 years of age with a BMI in the 99th percentile plus 5 units at screening. 11. The patient has a history of alcohol or illicit drug use disorder. 12. The patient has a history of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist. 13. The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding. 14. The male patient plans to father a child during the course of the study. 15. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study, including the ability to swallow the study medication capsules whole.

• Male or female, age above or equal to 18 years at the time of signing informed consent. Japan: Male or female, age above or equal to 20 years at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus
• HbA1c less than or equal to 10% (less than or equal to 86 mmol/mol)
• Renal impairment defined either by: 1. serum creatinine-based eGFR greater than or equal to 50 and less than or equal to 75 mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 300 and less than 5000 mg/g or 2. serum creatinine-based eGFR greater than or equal to 25 and less than 50 mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 100 and less than 5000 mg/g
• Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks prior to the date of the laboratory assessments used for determination of the inclusion criteria for renal impairment and kept stable until screening
• Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations
• Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to screening
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening
• Presently classified as being in New York Heart Association (NYHA) Class IV heart failure
• Planned coronary, carotid or peripheral artery revascularisation
• Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal dialysis
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination

• Signed informed consent given by the subject or the subject's parent/legal guardian for those under 18 years of age or the age of consent by local regulation.
• Male and female subjects with a suspected or confirmed UCD diagnosis of any subtype, except NAGS deficiency.
• Suspected diagnosis is defined as having experienced a HAC or a documented high ammonia of >=100 µmol/L
• Confirmed diagnosis is determined via enzymatic, biochemical, or genetic testing.
• Requires nitrogen-binding agents according to the judgment of the Investigator
• Birth and older.
• All females of childbearing potential and all sexually active males must agree to use an acceptable method of contraception from signing the informed consent throughout the study and for 30 days after the last dose of study drug. Acceptable forms of contraception are (oral, injected, implanted or transdermal), tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier methods. Abstinence is an acceptable form of birth control, though appropriate contraception must be used if the subject becomes sexually active.
• Subject has received chronic treatment with an oral phenylbutyrate (RAVICTI, NaPBA, Pheburane, or other) longer than 14 consecutive days within one year prior to enrollment.
• Temporary use of NaPBA for acute management of a hyperammonemic crisis in the past is acceptable.
• Any concomitant illness (e.g., malabsorption or clinically significant liver or bowel disease) which would preclude the subject's safe participation, as judged by the Investigator.
• Has undergone liver transplantation, including hepatocellular transplant.
• Subjects on NaBz at Baseline will be excluded if they are viewed by the Investigator as being unable to undergo NaBz transition to a PAA prodrug during the Initial Treatment Period.
• Known hypersensitivity to PBA or any excipients of the NaPBA/PBA formulations.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed at the Baseline Visit prior to the start of study drug.

Inclusion Criteria : 1. Patient is undergoing investigation of recent confirmed hematuria (by either flexible or rigid cystoscopy/TURBT), including hematuria subjects referred due to suspicious/positive imaging, in order to determine the presence of urothelial carcinoma. 2. Able to provide a voided urine sample of the required minimum volume 3. Able to give written consent 4. Able and willing to comply with study requirements 5. Aged 18 years or older Exclusion Criteria 1. Prior history of bladder malignancy, prostate or renal cell carcinoma 2. Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation, urethral dilation) in the 14 days before urine collection, 3. History of glomerulonephritis, nephrosis or other renal inflammatory disorders, recent history of pyelonephritis 4. Previous alkylating based chemotherapy 5. Pregnancy

• STEP I REGISTRATION CRITERIA
• Histologically documented renal cell carcinoma with clear cell component, including patients who have sarcomatoid features.
• Any metastatic disease, including visceral, lymph node, other soft tissue and bone, measurable per RECIST 1.1.
• Measurable disease as defined in the protocol.
• Must be intermediate or poor risk patient per International Metastatic Renal Cell Carcinoma Database (IMDC) criteria (1 or more of the following: Karnofsky performance status [KPS] < 80, < 1 year from diagnosis [including initial nephrectomy] to systemic treatment for metastatic disease, hemoglobin less than lower limit of normal [LLN], corrected calcium concentration greater than upper limit of normal [ULN], absolute neutrophil count greater than ULN, platelet count > ULN).
• Central nervous system (CNS) disease permitted, if stable and not otherwise causing symptoms or needing active treatment.
• Karnofsky performance status >= 70%.
• No prior treatment with PD-1, PD-L1, or CTLA-4 targeting agents (including but not limited to nivolumab, pembrolizumab, pidilizumab, durvalumab, atezolizumab, tremelimumab, and ipilimumab), or any other drug or antibody specifically targeting T-cell co-stimulation or checkpoint pathways. The only exception is for prior treatment with nivolumab or other PD-1/PD-L1/CTLA-4 targeting therapy on pre- or post-operative trials, as long as > 1 year since completion of systemic therapy.
• No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 [> 28 days] and prior adjuvant sunitinib > 180 days since completion and prior immunotherapy as above are allowed).
• No cancer therapy less than 28 days prior to registration; this includes radiation therapy, except for bone lesions less than 14 days prior to registration. There must be a complete recovery and no ongoing complications from radiotherapy.
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =< 14 days prior to registration is required.
• Age >= 18 years
• Absolute neutrophil count (ANC) >= 1,500/mm^3.
• Platelet count >= 100,000/mm^3.
• Hemoglobin >= 8 g/dL.
• Calculated (Calc.) creatinine clearance >= 30 mL/min.
• Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1.
• Total bilirubin =< 1.5 x upper limit of normal (ULN).
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 2.5 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present.
• STEP 2 REGISTRATION ELIGIBILITY CRITERIA
• Successful completion of at least 1 cycle of ipilimumab/nivolumab.
• Resolution of any treatment-related adverse events to grade 1 or less per dose modification section (this criteria does not include any adverse events [AEs] not attributable to treatment which are present due to disease). Exceptions for this criteria include patients receiving replacement hormone treatments (such as levothyroxine for treatment-related hypothyroidism or glucocorticoid replacement for adrenal insufficiency). Please contact study chair if further discussion is needed.
• No more than 70 days from last dose of ipilimumab/nivolumab.
• Active autoimmune disease requiring ongoing therapy.
• Ongoing acute toxicity > grade 2 from previous treatment.
• History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies.
• History of human immunodeficiency virus (HIV) or active hepatitis B/C, or active tuberculosis (purified protein derivative [PPD] response without active TB is allowed).
• Concurrent use of immunosuppressive medication including prednisone above 10 mg daily.
• Uncontrolled adrenal insufficiency.
• Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP > 90 mmHg).
• Major surgery less than 28 days prior to registration.
• Any serious non-healing wound, ulcer, or bone fracture within 28 days prior to registration.
• Any arterial thrombotic events within 180 days prior to registration.
• Clinically significant hematuria, hematemesis, or hemoptysis within 12 weeks prior to registration.
• Cavitating pulmonary lesions or known endotracheal or endobronchial disease manifestations.
• Lesions encasing or invading any major blood vessels (this does not include tumor thrombus extending into/through renal vein/inferior vena cava [IVC]). Patients with tumor thrombus extending into/through renal vein are considered eligible.
• Moderate of severe hepatic impairment (Child-Pugh B or C).
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) in the 180 days prior to registration. (Any asymptomatic, treated pulmonary embolism or asymptomatic, treated deep venous thrombosis > 30 days prior to registration allowed).
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms.
• Unstable cardiac arrhythmia within 6 months prior to registration.
• Any gastrointestinal (GI) bleeding =< 180 days, hemoptysis, or other signs of pulmonary hemorrhage =< 90 days prior to registration.
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration.
• Active peptic ulcer disease, inflammatory bowel disease, or malabsorption syndrome within 28 days prior to registration.
• Untreated hypothyroidism, evidence of pancreatitis, history of organ transplant, or history of congenital QT syndrome.
• Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g., clopidogrel) within 5 days of registration. 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, apixaban. Allowed also in patients with known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Significant cardiac ischemia events (ST elevation myocardial infarction [STEMI] or non-ST elevation myocardial infarction [NSTEMI]) within 6 months or active NY Heart Association class 3-4 heart failure symptoms

Idiopathic uric acid nephrolithiasis, with last stone analysis showing that stone has >90% uric acid in composition Age >21 years Any gender, race/ethnicity (from weight loss), but weight <165 Kg (to fit into MR instrument); eGFR>60ml/min/1.73 m2 Bariatric surgery, chronic diarrhea, recurrent UTIs current insulin use use of a thiazolidinedione in past 2 years contraindication to thiazolidinedione use (liver dz, pedal edema, CHF NYHA class III/IV, no contraception)

Key
• Diagnosis of ISN/RPS 2003 Class III or IV LN as evidenced by renal biopsy performed within 6 months. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
• Urine protein to creatinine ratio greater than or equal to (>/=) 1 on a 24-hour collection
• Other inclusion criteria may apply Key
• Pregnancy or breastfeeding
• Severe renal impairment or the need for dialysis or renal transplantation
• Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
• Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude patient participation
• Known active infection of any kind or recent major episode of infection
• Intolerance or contraindication to study therapies
• Other exclusion criteria may apply

• Written informed consent obtained before any assessment.
• Male or female patient ≥ 18 years old.
• Up to date vaccination as per local immunization schedules.
• Recipients of a kidney transplant
• Recipients of a primary kidney transplant from a heart-beating deceased, living unrelated or non-HLA identical living related donors.
• Multi-organ transplant recipients or prior kidney transplant.
• Recipients of an organ from a non-heart beating donor.
• Recipient of an organ from an HLA identical living related donor.
• ABO incompatible or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant
• Recipients of kidneys from donors who are older than 65 years.
• Recipients of kidneys from donors with terminal serum creatinine > 2 mg/dL.
• Patients at high immunological risk for rejection
• Patient who is anti-HIV positive, HBsAg-positive or anti-HCV positive (without proof of sustained viral response (SVR) after anti-HCV treatment).
• Recipient of a kidney from a donor who tests positive for HIV, HBsAg/HBc positive or HCV.
• A negative Epstein Barr virus (EBV) test.
• Evidence of advanced liver disease (Child-Pugh C), or any sign of liver decompensation.
• Patient with severe systemic infections, current or within the two weeks prior to randomization.
• History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases, with the exception of localized excised non-melanomatous skin lesions.

• STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
• STEP 1 REGISTRATION: Participants must have primary tumor in place
• STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:
• Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast Scans must be performed within the following timeframes:
• Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
• Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment
• STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
• STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
• STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
• STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
• STEP 1 REGISTRATION: As 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
• STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
• CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2 • STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
• Stable disease
• Partial response
• The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1
• STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
• STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
• STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
• 2 infusions of nivolumab + 1 infusion of ipilimumab
• 2 infusions of pembrolizumab
• 2 infusions of avelumab
• STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
• STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
• STEP 2 REGISTRATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• STEP 2 REGISTRATION: Serum creatinine =< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)
• STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
• STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:
• Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
• Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:
• Treatment naive participants must not have received any pre-randomization treatment.
• Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:
• 4 infusions of nivolumab
• 4 infusions of ipilimumab
• 4 infusions of pembrolizumab
• 7 infusions of avelumab
• STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:
• Treatment naive participants must not have received any immunotherapy within a year of registration
• Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
• STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
• STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
• STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
• STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
• STEP 2 REGISTRATION: 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 participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years

• Candidate for ureteroscopy with laser lithotripsy;
• Presence of renal stone(s);
• Be willing and able to return for all study-related follow up procedures; and,
• Have been informed of the nature of the study, agreeing to its requirements, and have signed the IRB approved informed consent.
• BMI > 45;
• Significant comorbidities;
• Bladder, ureteral or kidney abnormalities;
• Pregnant individuals; or
• Unable to meet the treatment and follow up protocol requirements.

• The patient must have histologic or cytologic evidence of a malignant solid tumor and must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy likely to result in clinical benefit.
• The patient must have advanced disease, defined as cancer that is either metastatic, OR locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered feasible).
• The patient must have disease that is measurable by standard imaging techniques, per the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), or evaluable per RECIST 1.1. (For patients with prior radiation therapy, measurable lesions must be outside of any prior radiation field[s], unless disease progression has been documented at that disease site subsequent to radiation.)
• The patient is ≥18 years old.
• The patient has an ECOG PS of 0-2.
• The patient has adequate baseline organ function, as demonstrated by the following:
• Serum creatinine ≤1.5 × institutional upper limit of normal (ULN) or calculated creatinine clearance >30 mL/min.
• Serum albumin ≥2.5 g/dL.
• Bilirubin ≤1.5 × institutional ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × institutional ULN (patients with hepatic metastases must have AST/ALT ≤5 times ULN).
• International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤1.5 × ULN.
• The patient has adequate baseline hematologic function, as demonstrated by the following:
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L
• Hemoglobin ≥8 g/dL, with no red blood cell (RBC) transfusions within the prior 14 days.
• Platelet count ≥100×10⁹/L, with no platelet transfusions within the prior 14 days.
• If the patient is a woman of child bearing potential (WOCBP), she has had a negative serum or urine pregnancy test within 1 week prior to treatment.
• The patient (male and female) agrees to use acceptable contraceptive methods for the duration of time on the study, and continue to use acceptable contraceptive methods for 1 month after the last dose of SL-801.
• The patient has signed informed consent prior to initiation of any study-specific procedures or treatment.
• The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.
• The patient has persistent clinically significant ≥Grade 2 toxicities from previous anticancer therapy (excluding Grade 2 chemotherapy-related neuropathy which is permitted, and excluding Grade 2-3 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the Investigator, and can be managed with available medical therapies).
• The patient has received treatment with chemotherapy, external-beam radiation, or other systemic anticancer therapy within 28 days prior to study entry (Patients with advanced prostate cancer who are receiving luteinizing hormone releasing hormone [LHRH] agonists are permitted onto the study and should continue use of these agents during study treatment).
• The patient has received treatment with an investigational systemic anticancer agent within 28 days prior to C1D1.
• The patient has previously received treatment with SL-801 or another investigational agent that inhibits the XPO1/CRM1 pathway.
• The patient has an additional active malignancy that may confound the assessment of the study endpoints. Patients with a past cancer history (active malignancy within 2 years prior to study entry) with substantial potential for recurrence must be discussed with the Sponsor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia), organ-confined prostate cancer with no evidence of progressive disease.
• The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure [Appendix 1], uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the patient at significant risk for pulmonary complications during the study.
• The patient has known active or suspected brain or leptomeningeal metastases. (Central nervous system [CNS] imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement). Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 3 months following radiation therapy or other locoregional ablative therapy to the CNS.
• The patient is receiving immunosuppressive therapy for prophylaxis following a prior organ transplant (solid organ or allogeneic stem cell) or management of immune-mediated toxicities due to immunotherapy. Low-dose corticosteroid (defined as < 10mg/day of prednisone or equivalent) therapy is permitted.
• The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements.
• The patient is pregnant or breast feeding.
• The patient has known positive status for human immunodeficiency virus active or chronic Hepatitis B or Hepatitis C.
• The patient is oxygen-dependent.
• The patient has any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.

1. Aged ≥ 12 years 2. At least 1 symptomatic stone event (passage or procedural intervention) within 3 years prior to enrollment 3. Low 24‐hr urine volume 1. ≥18 years old: <1.8 L/day 2. <18 years old: <20 ml/Kg/day up to 1.8L/day 4. Able to provide informed consent (parental permission for children) 5. Owning and willing to use a smartphone or other device (e.g., tablet) compatible with the study‐provided wireless enabled "smart" bottle 1. Spinal cord injury 2. Currently undergoing active treatment for cancer except basal cell skin cancer, or patients with a history of cancer who completed their initial therapy <1 year before screening. 3. Known infectious (struvite), monogenic or other causes of stone disease for which therapies are likely to significantly alter course of stone disease 1. Cystinuria 2. Primary hyperoxaluria 3. Primary xanthinuria 4. Primary hyperparathyroidism 5. Sarcoidosis 6. Medullary sponge kidney 4. History or presence of hyponatremia (serum sodium <130 mmol/L) or hypo‐osmolality (serum osmolality <275 mosm/kg) 5. Study participants with comorbidities that preclude high fluid intake or prior surgery precluding high fluid intake or leading to GI fluid losses 1. History of or current Crohn's disease, ulcerative colitis, short gut syndrome (e.g. ileostomy, bowel bypass surgery to treat obesity, small bowel resection), chronic diarrhea, or GI tract ostomy. 2. History of malabsorptive (e.g., Roux‐en‐Y gastric bypass) or restrictive (e.g., sleeve gastrectomy) bariatric surgery procedures 3. Congestive heart failure i. NYHA class II or greater, and/or ii. Hospital admission in the past year for heart failure d. Lung disease with a home oxygen requirement e. Chronic kidney disease (eGFR <30 ml/min/1.7 m2 over a 3‐month period) i. For adults (age ≥18), we will use the CKD‐Epi equation which requires the measurement of serum creatinine only. ii. For children (age <18), we will use the bedside Schwartz (CKiD) formula. f. Nephrotic syndrome (>3.5 grams of protein per 24 hours) g. Cirrhosis with ascites 6. Women who are currently pregnant or planning pregnancy within 2 years. 7. Renal transplant recipient 8. Bedridden study participants (ECOG ≥ 3) 9. Uncorrected anatomical obstruction of the urinary tract 10. History of recurrent urinary tract infections (> 3 UTI/year proven by urine culture) 11. Exclusions due to medication use: 1. Chronic use of lithium 2. Long‐term glucocorticoid use (> 7.5 mg prednisone daily for > 30 days prior to enrollment) 3. Intake of narcotic medication on a daily basis for >30 days prior to enrollment 4. Supplemental Vitamin C (> 1 g daily) 12. Individuals with stones that have developed after the initiation of medications that are strongly associated with USD such as carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide), high dose vitamin C (> 1 g daily), high dose calcium supplementation (> 1,200 mg daily) AND who have discontinued or plan to discontinue these medications. 13. Individuals taking medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir) AND who have discontinued or plan to discontinue these medications. Note: Individuals who are on long‐term medications that increase the risk of stone disease, who cannot stop these medications due to other chronic conditions (e.g., HIV) and who may reduce their risk for stone recurrence through increased fluid intake, will be eligible to participate in the trial. Examples of these medications include: 1. Carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide) 2. Medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir). 14. Study participants <2 yrs life expectancy 15. Non‐English Speakers 16. History of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) 17. Anatomical urologic abnormalities including ileal conduits, horseshoe kidney, megaureter or solitary kidney. 18. Psychiatric conditions impairing compliance with the study 19. Vulnerable population (prisoner and/or cognitive impairment that the investigator feels will impact the study participant's ability to participate in the protocol) 20. Individual who will be unable to participate in the protocol in the judgment of the investigator.

1. Orthotopic heart transplantation 2. Age < 21 years at time of transplant 3. Stable immunosuppression at the time of randomization with no contraindication to everolimus, tacrolimus, or mycophenolate mofetil 4. Planned follow-up at a study site for the 30 month duration of the study. 5. Subject or legal adult representative capable of providing informed consent (in general, assent will be sought for children aged 12 years or older). 1. Multi-organ transplant (e.g. heart-lung or heart-liver). 2. Known hypersensitivity to everolimus, sirolimus, tacrolimus or mycophenolate mofetil (MMF), or to components of the drug products. 3. Patients on maintenance corticosteroid therapy exceeding a dose equivalent of prednisone 0.1 mg/kg/day at randomization. 4. High-risk for rejection defined as active rejection, recurrent (≥ 2 episodes of grade 2R rejection) cellular rejection, recurrent rejection (≥ 2 episodes of any grade) with hemodynamic compromise, steroid-resistant rejection or unresolved antibody-mediated rejection during the first 6 months post-heart transplant 5. Graft dysfunction (LVEF <40% or wedge pressure >22 mmHg or cardiac index <2.2 L/min/m2) 6. Stage 4 or 5 CKD (eGFR <30 ml/min/1.73 m2) or moderate proteinuria (urine protein to urine creatinine ratio >0.5 mg/mg). 7. Active infection requiring hospitalization or treatment dose medical therapy. 8. Patients with ongoing wound healing problems, clinically significant wound infection requiring continued therapy or other severe surgical complication in the opinion of the Site Principal Investigator. 9. Fasting Serum Cholesterol ≥300 mg/dL OR greater than or equal to 7.75 mmol/L, AND fasting triglycerides ≥2.5x the upper limit of normal (ULN). Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication, and reduction of serum cholesterol and triglyceride levels to below exclusion ranges is confirmed. 10. Uncontrolled diabetes mellitus. 11. Diagnosis of post-transplant lymphoproliferative disorder (PTLD) during the first 6 months post-heart transplant. 12. History of non-adherence to medical regimens. 13. Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) and cannot discontinue the treatment 14. Patients who are pregnant or breast-feeding or intend to get pregnant during the study period.

1. Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent:
• Dose-Escalation Stage:
• Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or
• Subjects with RCC (clear cell, non-clear cell histology) with or without prior systemic anticancer therapy
• Expansion Stage:
• Inoperable locally advanced or metastatic solid tumor (UC, RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC, CRC, H&N cancer, and DTC as outlined above) 2. Measurable disease per RECIST 1.1 as determined by the investigator. 3. Tumor tissue material available (archival or recent tumor biopsy) 4. Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. 5. Age eighteen years or older on the day of consent. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 7. Adequate organ and marrow function. 8. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception. 9. Female subjects of childbearing potential must not be pregnant at screening. 1. Prior treatment with cabozantinib or immune checkpoint inhibitors including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy except in Expansion Cohorts 5, 7,19 and 20. Other restrictions regarding prior therapy may apply. 2. Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks before first dose of study treatment. 3. Concomitant anticoagulation with oral anticoagulants. 4. Subject is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment. 5. Administration of a live, attenuated vaccine within 30 days before first dose of study treatment. 6. The subject has uncontrolled, significant intercurrent or recent illness, including, but not limited to, an active or history of autoimmune disease or immune deficiency; idiopathic pulmonary fibrosis, organizing pneumonia, pneumonitis; active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV), AIDS-related illness, acute or chronic hepatitis B or C infection, positive test for tuberculosis, moderate to severe hepatic impairment (Child-Pugh B or C). 7. Pregnant or lactating females. 8. Previously identified allergy or hypersensitivity to components of the study treatment formulations. 9. Diagnosis of another malignancy within 2 years before first dose of study treatment.