Criteria for Inclusion of Subjects: Hand and forearm amputees: 1. Male or female, age 18 and older, of any race or ethnicity 2. Able and willing to sign Consent 3. Able and willing to participate in all study activities including implantation, testing and explantation of the study device. 4. Able to communicate effectively in English without an interpreter After preliminary screening subjects will be assessed for the following inclusion criteria: 1. Patient has an existing myoelectric hand prosthesis and demonstrates proficiency during daily use 2. Overall and phantom pain are well-controlled and not incapacitating Criteria for Exclusion of Subjects: 1. If MR neurogram and EMG/NCS study show nerve or muscle dysfunction/injury at a higher level than anticipated based on the appearance of the physical amputation stump, the subject may be excluded from the study due to adverse neuromuscular anatomy which would preclude use of the proposed experimental electrode implants. The radiographs will be used to confirm suitability of the amputation stump configuration. If the bony anatomy of the amputation stump is found to be unsuitable, the patient may be excluded from the study. 2. Subjects who have a history of cardiac arrhythmia will be excluded from the study.

• 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

• 3
•7 years old
• male or female
• non-dominant upper extremity brachial plexus injury
• Botox injections to the affected extremity within the past 3 months
• Severe muscle contractures of affected extremity that restricts functional use of the arm and hand
• Concurrent cerebral palsy

Key Inclusion Criteria
• Patients ≥6 months and up to 60 months (1800 days) of age at time of dosing following diagnostic confirmation during screening period by genotype who demonstrate the ability to sit unassisted for 10 or more seconds but cannot stand or walk
• Diagnostic confirmation by genotype includes lab documentation of homozygous absence of SMN1 exon 7; with exactly three copies of SMN2
• Negative gene testing for SMN2 gene modifier mutation (c.859G>C)
• Onset of clinical signs and symptoms consistent with spinal muscular atrophy (SMA) at < 12 months of age
• Able to sit independently and not standing or walking independently. Definition of sitting independently is defined by the World Health Organization Multicentre Growth Reference Study (WHO-MGRS) criteria of being able to sit up unsupported with head erect for at least 10 seconds. Child should not use arms or hands to balance body or support position (Wijnhoven 2004)
• Be up-to-date on childhood vaccines that include palivizumab prophylaxis (also known as Synagis) to prevent respiratory syncytial virus (RSV) infections are also recommended in accordance with American Academy of Pediatrics (AAP 2009) Key Exclusion Criteria
• Current or historical ability to stand or walk independently
• Contraindications for spinal tap procedure or administration of intrathecal therapy or presence of an implanted shunt for the drainage of CSF or an implanted central venous (CNS) catheter
• Severe contractures as determined by designated Physical Therapist(s) at screening that interfere with either the ability to attain/demonstrate functional measures or interferes with ability to receive intrathecal (IT) dosing
• Severe scoliosis (defined as ≥ 50° curvature of spine) evident on X-ray examination
• Previous, planned or expected scoliosis repair surgery/procedure within 1 year of dose administration
• Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening while the patient is awake, or for high altitudes > 1000 m, oxygen saturation < 92% while the patient is awake
• Pulse oximetry saturation must not decrease ≥ four (4) percentage points between screening and highest value on day of dosing
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods (i.e., nasogastric tube or nasojejunal tube) or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion
• Active viral infection (includes human immunodeficiency virus (HIV) or serology positive for hepatitis B or C, or Zika virus)
• Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization within two (2) weeks prior to study entry
• Respiratory infection requiring medical attention, medical intervention or increase in supportive care of any manner within four (4) weeks prior to study entry
• Severe non-pulmonary/respiratory tract infection within four (4) weeks before study dosing or concomitant illness that in the opinion of the Principal Investigator (PI) creates unnecessary risks for gene transfer such as:
• Major renal or hepatic impairment
• Known seizure disorder
• Diabetes mellitus
• Idiopathic hypocalciuria
• Symptomatic cardiomyopathy
• History of bacterial meningitis or brain or spinal cord disease, including tumors, or abnormalities by magnetic resonance imaging (MRI) or computerized tomography (CT) that would interfere with the lumbar puncture (LP) procedures or CSF circulation
• Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
• Known allergy or hypersensitivity to iodine or iodine-containing products
• Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months of study dosing
• Inability to withhold use of laxatives or diuretics in the 24 hours prior to dose administration
• Anti-AAV9 antibody titers >1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay
• Should a potential patient demonstrate anti AAV9 antibody titer > 1:50, he or she may receive retesting within 30 days of the screening period and will be eligible to participate if the anti AAV9 antibody titer upon retesting is ≤ 1:50
• Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin > 2 × ULN, creatinine ≥ 1.0 mg/dL, hemoglobin [Hgb] < 8 or > 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy. Patients with an elevated bilirubin level that is unequivocally the result of neonatal jaundice shall not be excluded
• Participation in recent SMA treatment clinical trial or receipt of an investigational or approved compound product or therapy received with the intent to treat SMA at any time prior to screening for this study
• Oral beta agonists must be discontinued 30 days prior to dosing.
• Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable and not a contraindication at any time prior to screening for this study
• Expectation of major surgical procedures during the 1-year study assessment period

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.

• 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. At least 18 years of age and up to 55 years (inclusive) of age at Baseline. 2. Clinical diagnosis of Multiple Sclerosis (MS) who have had Relapsing MS (RMS) no longer than 15 years from diagnosis. 3. Stable treatment with natalizumab for at least the prior six (6) months. 4. Stable disease activity over the prior six (6) months. 5. All hematological parameters and biochemical parameters deemed stable or transient in nature. 6. Able to understand and give written informed consent. 1. Patients with a clinical relapse requiring systemic steroid treatment within the prior six (6) months. 2. Patients treated with any other MS therapy other than natalizumab; or treated with clemastine fumarate. 3. Patients with a history of significant other major medical condition that may interfere with the conduct of the study or interpretation of the study results. 4. Patients who may have difficulty complying with the protocol and/or study procedures. 5. Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation. 6. Patients with clinically significant hepatic or renal dysfunction or clinical laboratory findings that would limit the interpretability of change in liver or kidney function, or those with low platelet counts (< 150 x 109 per liter) or eosinophilia (absolute eosinophil count of ≥500 eosinophils per microliter). 7. Patients with a prior history of, or positive serological assay for the presence of HIV infection, or laboratory evidence of active or chronic infection with hepatitis C (HCV) or hepatitis B (HBV). 8. Patients participating in any other investigational drug trial or using an investigational drug (within 12 weeks prior to screening and thereafter) 9. Positive screen for drugs of abuse or known alcohol abuse. 10. Females who are pregnant, have a positive pregnancy test, are nursing, or who plan to get pregnant during the course of this clinical trial or within 6 months of the end of this trial. 11. Women of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control during the study and for 6 months following completion of study participation. 12. Patients with implanted metal objects in their body that may be affected by an MRI procedure. 13. Patients who are claustrophobic or otherwise unlikely to be able to complete the MRI scanning procedures. 14. Patients with a history of gold allergy. 15. Patient is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. 16. Any active ophthalmological cause for retinal damage other than MS or based on the Investigator's judgment any other ophthalmic diseases that would confound the study results or optical coherence tomography assessment. 17. PRN use of stimulant medications including: amphetamine, dextroamphetamine, lisdexamfetamine, methylphenidate, or modafinil.

1. Male or female, 18 to 80 years of age (inclusive). 2. Lower limb spasticity due to stroke or traumatic brain injury (TBI) that occurred at least 6 months prior to study. May have lower limb monoplegia or hemiplegia. 3. Able to walk (with or without the use of a walking assistive device). 4. Modified Ashworth Scale (MAS) score greater than or equal to 2 in the ankle plantar flexors of the affected lower limb at screening and at baseline. 1. Quadriplegia/tetraplegia, lower limb diplegia or triplegia. 2. Uncontrolled epilepsy with a seizure(s) within the last year. 3. Neuromuscular disorders including, but not limited to, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), multiple sclerosis (MS), myasthenia gravis, or muscular dystrophy. 4. History of major joint contracture(s), in which, based on Investigator assessment, the contracture(s) significantly contributes to joint immobility in the target limb. 5. Known hypersensitivity to botulinum toxins type A or B or to any MYOBLOC solution components. 6. Application of an ankle-foot orthosis (AFO) within 30 days before screening. Subjects regularly using an AFO 30 days or more before screening must be willing to maintain use of the AFO through Week 4 of the DBP of the study. 7. Prior botulinum toxin type A (BoNT/A) or B (BoNT/B) treatment in the lower limb identified for treatment within 24 weeks before screening. Prior BoNT/A or BoNT/B treatment in areas other than the target limb is not exclusionary but must have occurred at least 12 weeks before screening. Prior toxin exposure must have been well-tolerated and without any significant long-term side effects in the case of repeated prior exposure. 8. Severe dysphagia (i.e., inability to swallow liquids, solids, or both without choking or without medical intervention), or dysphagia with a history of aspiration pneumonia, within 6 months before screening. 9. Obstructive pulmonary disease with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <70%. 10. Slow vital capacity <60% of predicted.

• Signed informed consent form by patients and/or patients' parents/legal guardians and age appropriate assent form by the patients obtained before any study specific procedure
• Male or female patients from 6 months to ≤ 21 years old at the time of study enrollment
• Confirmation of diagnosis:
• Phase I: Patients must have histologic verification of a solid tumor or lymphoma malignancy at diagnosis, with measurable or evaluable disease, for which there is no standard curative anti-cancer treatment or treatment is no longer effective and must have received ≥ 1 prior line of therapy.
• Phase II: patients must have histologically verified tumor at initial diagnosis and radiologically or histologically confirmed status at inclusion as indicated in the following: neuroblastoma, osteosarcoma, rhabdomyosarcoma or Ewing sarcoma.
• In Phase II, patients with solid tumors must have measurable disease (evaluable disease is acceptable for neuroblastoma and Ewing sarcoma). Tumor assessment will be done via computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT). Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the lesion. Bone scans (if clinically indicated) should be obtained within ≤ 4 weeks prior to the start of treatment.
• Performance level: Lansky ≥ 50% for patients ≤ 16 years of age and Karnofsky ≥ 50% for patients > 16 years of age.
• Adequate bone marrow, renal and liver function.
• Active or uncontrolled infection (National Cancer Institute (NCI)-CTCAE Grade ≥ 2).
• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator).
• Diabetes mellitus.
• Uncontrolled arterial hypertension despite optimal medical management (per institutional guidelines).
• Patients with central nervous system (CNS) malignancies.

• 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.

• Any patient of the Children's Medical Center CCBD
• 5-12 years of age
• Patient requiring their port accessed twice or more within a 6 months period
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Subjects younger than 5 and older than 12
• Patients requiring recovery in PICU or sites other than PACU
• If parents or subject is not willing to participate
• Subjects with severe developmental delays and subjects with developmental challenges preventing them from keeping the VR device on are also excluded
• Patients who will not be in CCBD for port access at least twice in 6 months

• 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.

• Has completed a study of SRP-5051 and continues to meet the Eligibility Criteria of Study 5051-102.
• Initiation or change of dosing (except for modifications to accommodate changes in weight or changes in standard of care) since completing a study administering SRP-5051 and while participating in this study for any of the following: angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocking agents (ARBs), beta-blockers, potassium and steroids*.
• Requires antiarrhythmic and/or diuretic therapy for heart failure.
• Use of any herbal medication/supplement containing aristolochic acid.
• Treatment with any experimental therapy since entering original study or any experimental gene therapy for the treatment of DMD at any time.
• Participation in an interventional clinical trial since completing original study. Other inclusion/exclusion criteria apply. * The dose of steroids must remain constant except for modifications to accommodate changes in weight.

• 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

• Aged =>50 years to <85 years
• Shoulder pain and/or loss of range of active motion, strength or function
• MRI-confirmed partial- or full-thickness supraspinatus and/or infraspinatus tear of 4cm or less in longitudinal dimension
• Medically fit for surgery, defined as Category I-III per American Society of Anesthesiologists (ASA) Physical Status Classification
• Ability and willingness to provide informed consent
• Primary diagnosis is something other than a rotator cuff tear
• History (in last 2 years) of shoulder fracture involving the humeral head on affected side
• Previous rotator cuff surgery on affected side
• Isolated subscapularis &/or teres minor tear on affected side
• Acute rotator cuff tear caused by a severe trauma
• Shoulder used as a weight-bearing joint
• Contraindication to MRI (claustrophobia, pacemaker, pregnancy, shoulder implant, etc.)
• Glenohumeral osteoarthritis on xrays/MRI
• Grade 4 fatty infiltration of rotator cuff (any tendons)
• Candidate for shoulder arthroplasty at baseline
• Non-English speaking

• Male and females between the ages 14 and 58 years at the time of consent
• Closed physeal plates at the time of consent
• Intermetatarsal angle is between 10.0 ̊
•22.0 ̊
• Hallux valgus angle is between 16.0 ̊
•40.0 ̊
• Willing and able to adhere to early weight-bearing instructions post-operatively
• Capable of completing self
•administered questionnaires
• Acceptable surgical candidate, including use of general anesthesia
• Female patients must be of non-child bearing potential or have a negative pregnancy test within 7 days prior to index procedure
• Willing and able to schedule index procedure within 3 months of consent and able to return for scheduled follow-up visits
• Willing and able to provide written informed consent
• Previous surgery for hallux valgus on operative side
• Previous surgeries on operative foot involving fusion of foot or ankle joints (other than hammertoe or lesser toes/digits)
• Additional arthrodesis outside the first tarsometatarsal joint (other than: arthrodesis between the medial cuneiform and intermediate cuneiform and/or base of 2nd metatarsal; arthrodesis of hammertoe proximal interphalangeal joint or lesser toes/digits)
• Moderate or Severe osteoarthritis of the MTP joint based on radiographic imaging (including lack of evident crista) or positive grind test
• Symptomatic flatfoot or asymptomatic flatfoot (defined as calcaneal inclination <5 ̊and talonavicular subluxation/uncovering >50%)
• BMI >40 kg/m²
• Current nicotine user, including current use of nicotine patch
• Current clinical diagnosis of diabetes with fasting plasma glucose > 126 mg/dL and/or HbA 1c ≥7.0
• Current clinical diagnosis of peripheral neuropathy or by assessment on 4
•point monofilament test
• Current clinical diagnosis of fibromyalgia
• Current clinical diagnosis of Complex Regional Pain Syndrome/Reflex Sympathetic Dystrophy (CRPS/RSD)
• Current uncontrolled hypothyroidism
• Previously sensitized to titanium
• Currently taking oral steroids or rheumatoid biologics
• Currently taking immunosuppressant drugs
• Insufficient quantity or quality of bone to permit stabilization, conditions that retard healing (not including pathological fractures) and conditions causing poor blood supply such as peripheral vascular disease
• Active, suspected or latent infection in the affected area
• Use of synthetic or allogenic bone graft substitutes
• Current diagnosis of metatarsus adductus (defined as MAA ≥ 23 ̊)
• Scheduled to undergo a same
•bilateral procedure. Patient agrees to refrain from the Lapiplasty® Procedure (or other hallux valgus procedures) on contralateral foot for minimum of 6 months post index procedure
• Patient has previously been enrolled into this study for a contralateral procedure
• Scheduled for any concomitant procedure that would alter patient's ability to early weight-bear post-procedure
• Patient is actively involved with a workman's compensation case or is currently involved in litigation
• Patient is currently or has participated in a clinical study in the last 30 days prior to signing
• Patient has a condition or finding that, in the opinion of the Investigator, may jeopardize the patient's well-being, the soundness of this clinical study, or could interfere with provision of informed consent, completion of tests, therapy, or follow-up

1. At least 18 years of age and up to 55 years of age (inclusive) at Screening. 2. Clinical diagnosis of Relapsing Multiple Sclerosis (meeting McDonald criteria, 2010) who have had RMS no longer than 15 years from diagnosis. 3. Maximum Best Corrected High Contrast Visual Acuity (BC-HCVA) deficit on the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart of 20/200 (6/60 metric) in both eyes. a. BC-HCVA is defined as the last line on the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart that a patient is able to read three (3) or more letters correctly. 4. Best Corrected Low Contrast Letter Acuity (BC-LCLA) (by 2.5% Sloan Chart) must be 20/40 (6/12 metric) (inclusive) or worse in the affected eye and 20/32 (6/9.5 metric) or worse in the fellow eye; and the BC-LCLA must be worse than BC-HCVA for the respective value in both eyes. a. BC-LCLA is defined as the last line on the 2.5% Sloan Chart that a patient is able to read three (3) or more letters correctly. 5. Retinal Nerve Fiber Layer (RNFL) thickness ≥ 70 μm. 6. Stable disease activity based on the investigator's judgment over the previous 6 months. 7. All hematological parameters and biochemical parameters that fall outside the Within Normal Limits range must be assessed as Not Clinically Significant (NCS) and deemed stable or transient in nature. 8. Able to understand and give written informed consent. 1. History of AQP4, MOG Ab(+) status, or ≥ 3 segments lesion in the spinal cord. 2. Any diagnosis other than RMS that could explain the patient's signs and symptoms. 3. An acute optic neuritis episode within the prior 6 months. 4. Clinical relapse requiring systemic steroid treatment within the prior 3 months (pre- treatment with systemic steroids during the administration of disease-modifying therapies [DMT] may be allowed after discussion with the Sponsor's Medical Monitor but must not be administered within 30 days of a planned VEP or MRI assessment). 5. Unstable treatment with a disease-modifying therapy (DMT) defined as a treatment change within prior 3-months unless due to intolerability. 6. Current treatment with immunosuppressive or immunomodulatory therapy other than those approved for the treatment of MS. 7. Any treatment with drugs known or suspected of producing retinal or optic nerve toxicity including hydroxychloroquine, chloroquine, clofazimine, vigabatrin, or ethambutol. 8. Any history of ophthalmological cause for retinal damage other than MS (e.g. cataracts, uveitis, macular degeneration, macular exudate, macular edema, glaucoma, severe astigmatism, ocular trauma, neuromyelitis optica, ischemic optic neuropathy, congenital nystagmus, retinal detachment, amblyopia, optic disk drusen). 9. Severe refractive defects: refractive errors (-6 dioptres to +6 dioptres or more in either eye, or axial eye length >26 mm), hypermetropia (> 6 dioptres; cylinder > 3 dioptres); or based on the investigators judgment any other ophthalmic diseases that would confound the study results or assessment of Visual Evoked Potential (VEPs), Best Corrected Visual Acuity (BCVA), Low Contrast Letter Acuity (LCLA), or Optical Coherence Tomography (OCT). 10. History diabetic retinopathy or a previous diagnosis of Diabetes Mellitus or history of prior impaired fasting glucose ≥126 mg/dL (or ≥ 200 mg/dL after oral glucose tolerance test). 11. History of human immunodeficiency virus (HIV), hepatitis C (HepC) virus antibody, or hepatitis B (HepB) virus antibody. 12. History of gold allergy. 13. Patients taking stimulant medications (including: amphetamine, dextroamphetamine, lisdexamfetamine, methylphenidate, or modafinil) who have not been on a stable dose greater than or equal to 30 days. Changes to dose will not be allowed during the course of the trial). 14. Patients taking clemastine fumarate, 4-aminopyridine (fampridine), or high dose Biotin (>300 mg/day). 15. Females who have a positive serum pregnancy test result at Screening or Baseline, or who are pregnant, breastfeeding, or planning to conceive during the study or within 180 days after study completion. 16. History or evidence of substance abuse or alcohol abuse within 5 years prior to Screening, including alcoholism; or severe tobacco use (>1 pack/day). 17. Clinical history of toxic neuropathy (e.g., secondary to treatment with ethambutol, isoniazid, linezolid, gentamycin, chloramphenicol, vincristine, or penicillamine). 18. Current enrollment in any other drug or device treatment study within 3 months prior to Baseline. Participation in an observational non-interventional study (i.e., no drug or device therapy) is not an exclusion criterion. 19. Inability to undergo any planned study procedures such as LCLA, VEP, MRI, or OCT; history of severe hypersensitivity to gadolinium-DTPA or reduced renal clearance (GFR must be ≥ 45 mL/min at Screening), claustrophobia; or inability to comply with study requirements based on Investigator judgment. 20. Patients with clinically significant hepatic or renal dysfunction or clinical laboratory findings that would limit the interpretability of change in liver or kidney function, or those with low platelet counts (< 150 x 10^9 per liter) or eosinophilia (absolute eosinophil count of ≥ 500 eosinophils per microliter) at Screening. 21. Based on the investigator's judgment, concurrent chronic or acute illness or unstable medical condition that may deteriorate that could confound the results of safety assessments, increase risk to the patient, or lead to difficulty complying with the protocol; including severe disc edema or hemorrhage, any clinically significant cardiac, endocrinological, hematological, hepatic, immunological, metabolic, urological, pulmonary, neurological (any progressive neurological disorder other than RRMS), dermatological, psychiatric (any untreated or unstable psychiatric disease including depression, bipolar and psychosis), renal, severe allergic or anaphylactic reactions, autoimmune, or other major confounding diseases. 22. Any history of previous malignancy, with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix, post documented full resections, with clean margins. 23. Patient is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation.

Main 1. Diagnosis of Myasthenia Gravis (MG) supported by a positive serologic test for anti-AChR or anti-MuSK antibodies at screening. 2. Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV at screening. 3. Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of 6 or greater at screening, with at least 4 points attributed to nonocular items. 4. If receiving immunosuppressive drugs (ie, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, cyclophosphamide), therapy must be ongoing for at least 6 months, with stable dosing ongoing for at least 3 months before screening. Participants receiving azathioprine must be on a stable dose for at least 6 months before screening. 5. If receiving oral corticosteroids, therapy must be ongoing for at least 3 months, with a stable dose at least 1 month before screening. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy, as opposed to pulse therapy. 6. If receiving cholinesterase inhibitors, therapy with a stable dose is required at least 2 weeks before screening. 7. The doses of concomitant standard background therapy must be expected to remain stable throughout the study unless dose reduction is required due to toxicities. Allowed background therapy is defined as no more than a cholinesterase inhibitor ± corticosteroid ± 1 steroid-sparing immunosuppressive drug (limited to azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide). Participants must be on at least one allowed background medication. Main 1. Presence of a thymoma (previous history of a fully encapsulated thymoma removed ≥ 12 months before screening is allowed) or history of invasive thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥ 5 years before screening. 2. History of thymectomy within 12 months before screening. 3. MGFA class I or V. 4. Received intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), or plasmapheresis/plasma exchange within 4 weeks before screening, or an expectation that any therapy besides the participants standard background therapies may be used for treatment of MG (eg, a rescue therapy) between screening and dosing. 5. Chronic obstructive pulmonary disease (COPD) or asthma with a pre-bronchodilatory forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note: FEV1 testing is required for participants suspected of having COPD or asthma. 6. Received rituximab, belimumab, eculizumab, or any monoclonal antibody for immunomodulation within 6 months before first dosing. Participants with prior exposure to rituximab must have CD19 counts within the normal range at screening. 7. Known autoimmune disease other than MG that could interfere with the course and conduct of the study. 8. Received a live vaccine within 4 weeks before screening or has any live vaccination planned during the study. 9. Opportunistic infection ≤12 weeks before initial study dosing or currently receiving treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks of study dosing is allowed, as long as the lesion has resolved without systemic therapy prior to Day 1.

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. 10. 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) 11. 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.

• Male or female:
• 2 years of age at 5 pediatric CMS study sites
• 10 years of age at other study sites.
• Confirmed physician diagnosis of LEMS, CMS or downbeat nystagmus.
• Completion of anti-cancer treatment at least 3 months (90 days) before treatment.
• Negative urine pregnancy test for females of childbearing potential at Screening.
• If sexually active and of childbearing potential, willing to use 2 acceptable methods of contraception from screening visit until 3 months after the last dose of investigational product. No adequate clinical data on exposed pregnancies are available for amifampridine. No nonclinical safety data are available regarding the effects of amifampridine on reproductive function. Amifampridine phosphate should not be used during pregnancy. It is unknown whether amifampridine is excreted in human breast milk. The excretion of amifampridine in milk has not been studied in animals. Amifampridine phosphate should not be used during breastfeeding.
• Any subject currently participating in studies LMS-002, LMS-002EXT, or CMS 001 is immediately eligible for enrollment into study EAP-001, as long as inclusion/exclusion criteria are still met.
• Willing and able to provide written informed consent after the nature of the study has been explained and before the start of any research-related procedures.
• History of epilepsy.
• CMS subtypes including slow-channel syndrome, LRP4 deficiency, and acetylcholinesterase deficiency.
• Known active brain metastasis. Patients with treated brain metastasis (radiotherapy and/or surgery) who have completed treatment for their brain metastasis >90 days before Screening, are neurologically stable (neurological symptoms grade <1), are on a stable dose of corticosteroids and have no evidence of new disease on magnetic resonance imaging (MRI) are eligible, provided they meet the other inclusion/exclusion criteria.
• Current use of dalfampridine (Ampyra®; 4-aminopyridine), and any form of 3,4 DAP other than the investigational product provided, such as amifampridine base and does not agree to discontinue use for the duration of the study.
• Use of guanidine hydrochloride within 7 days of starting amifampridine phosphate treatment.
• History of drug allergy to any pyridine-containing substances or any amifampridine phosphate excipients (i.e. microcrystalline cellulose, colloidal silicon dioxide or calcium stearate).
• Use of any other investigational product (other than 3,4 DAP or amifampridine phosphate) or investigational medical device within 30 days before starting treatment or requirement for any investigational agent before completion of all scheduled study assessments.
• An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormality(ies), in the opinion of the patient's personal physician.
• History of additional risk factors for torsade de pointes (e.g. history of surviving a near drowning due to loss of consciousness, family history of congenital QT syndrome, long QT syndrome, family history of unexplained early sudden death, or heart failure).
• Breastfeeding or pregnant or planning to become pregnant (self or partner). Male patients with breastfeeding partners are not excluded from the study.
• History of severe renal impairment or evidence of severe renal impairment at time of Screening on laboratory tests, specifically a creatinine clearance <30 mL/min (within 30 days) as calculated using the Cockcroft Gault formula.
• History at time of Screening of laboratory tests (within 30 days) indicating hepatic impairment: o In patients without liver metastases from cancer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or total bilirubin >1.5 × upper limit of normal (ULN).
• Any condition that, in the view of the Principal Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.

Inclusion: 1. Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma. Histopathology confirmation of EWSR1-ETS or FUS-ETS rearrangement is required or availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or refractory disease with no known bone marrow metastases and at least evaluable disease. 2. Age ≥2 and <21 years at the time of study entry. 3. Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age. 4. Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed). 5. Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits. 6. Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome. 7. Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component). 8. Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia. 9. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit. 10. Evidence of a personally signed and dated informed consent document indicating that the patient or a legally acceptable representative/parent(s)/legal guardian of minors, has been informed of all pertinent aspects of the study. Minor study patients also must provide age appropriate assent according to the local guidelines, where applicable. 11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures. Exclusion: 1. Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 :prior treatment with a CDK4/6 inhibitor or prior treatment with an IRN and/or TMZ-containing regimen. 2. Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination. 3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.) 4. Prior growth factors (including filgrastim) within 7 days before study entry or PEG-filgrastim within 14 days before study entry. 5. Radiation therapy within 14 days before study entry. 6. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas. 7. Previous high dose chemotherapy requiring stem cell rescue within 90 days or persistent AE >Grade 1. 8. Prior irradiation to >50% of the bone marrow (see Appendix 9). 9. Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry. 10. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries. 11. For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX. 12. Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days. 13. Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable. 14. Hereditary bone marrow failure disorder.Phase 2 portion patients with bone marrow involvement are excluded. 15. QTc >470 msec. 16. History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%. 17. Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy). 18. Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness. 19. Other severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study. 20. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study. 21. Fertile male patients and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 after the last dose of investigational product.

• Age 5 through 21 years old at the time of screening for Cohorts 1 and 2; Age ≥2 years old at the time of screening for Cohort 3.
• Documented diagnosis of 5q SMA.
• Diagnosed as later-onset (e.g., Type 2 or Type 3) SMA prior to receiving any treatment with therapy approved for SMA.
• Non-ambulatory patients must be able to sit independently (sits up straight with head erect for at least 10 seconds; does not use arms or hands to balance body or support position) per World Health Organization (WHO) motor milestones definition at screening.
• Ambulatory patients must have the ability to independently ambulate without aids or orthotics over 10 meters in 30 seconds or less at screening.
• Receiving the same background SMA therapy (e.g., on an approved survival motor neuron (SMN) upregulator therapy such as nusinersen, or not on any SMA therapy) for at least 6 months prior to screening and anticipated to remain on that therapy throughout the duration of the study.
• If receiving the SMN upregulator therapy nusinersen, must have completed the loading regimen and initiated maintenance dosing (i.e., completed at least one maintenance dose) with at least 4 weeks after the first maintenance dose having elapsed prior to screening.
• Nutritional status stable over the past 6 months and anticipated to be stable throughout the duration of the study.
• Have no physical limitations that would prevent the patient from undergoing motor function outcome measures throughout the duration of the study.
• Able to receive study drug infusions and provide blood samples through the use of a peripheral intravenous (IV) or a long-term IV access device that the patient has placed for reasons independent from the study throughout the duration of the study.
• Able to adhere to the requirements of the protocol, including travel to the study center and completing all study procedures and study visits.
• For patients who are expected to have reached reproductive maturity by the end of the study, adhere to study specific contraception requirements.
• Use of tracheostomy with positive pressure.
• Use of chronic daytime non-invasive ventilatory support for >16 hours daily in the 2 weeks prior to dosing, or anticipated to regularly receive such daytime ventilator support chronically over the duration of the study.
• Any acute or co-morbid condition interfering with the well-being of the patient within 14 days of screening, including active systemic infection, the need for acute treatment or inpatient observation due to any reason.
• Severe scoliosis and/or contractures at screening. Based on clinical judgement, any scoliosis or contractures present must be stable over the past 6 months, anticipated to be stable for the duration of the study and not prevent the patient from being evaluated on any functional outcome measures throughout the duration of the study.
• Pregnant or breastfeeding.
• Major orthopedic or other interventional procedure, including spine or hip surgery, considered to have the potential to substantially limit the ability of the patient to be evaluated on any functional outcome measures, within 6 months prior to screening, or anticipated for the duration of the study.
• Prior history of a hypersensitivity reaction to a monoclonal antibody (mAb) or recombinant protein bearing an Fc domain (such as a soluble receptor- Fc fusion protein).
• Use of systemic corticosteroids within 60 days prior to screening. Inhaled or topical steroids are allowed.
• Treatment with investigational drugs within 3 months prior to screening.
• Use of therapies with potentially significant muscle effects (such as androgens, insulin-like growth factor, growth hormone, systemic betaagonist, botulinum toxin, or muscle relaxants) or muscle-enhancing supplements within 60 days prior to screening.
• Patient has any other condition, which in the opinion of the Investigator may compromise safety or compliance, would preclude the patient from successful completion of the study, or interfere with the interpretation of the results.

• Adult patients ≥ 18 years
• Individuals presenting for major shoulder arthroscopy procedures at Ambulatory Services Center (Outpatient Surgery Center) -that include rotator cuff repair and biceps tenodesis
• Patient is able to provide informed consent to participate in the study.
• Allergy to amide local anesthetic, liposomal bupivacaine or other medication involving liposomal formulation
• Preexisting neurological deficits involving or potentially involving the ipsilateral brachial plexus
• Preexisting contralateral vocal fold paralysis or recurrent laryngeal paralysis
• Psychiatric or cognitive disorders that could interfere with perioperative evaluation including drug or alcohol abuse
• Chronic pain conditions
• Preoperative opioid consumption greater than 20 mg oral morphine equivalent.
• Any contraindication to interscalene nerve block including any local disorder of the skin where blockade is to be performed which would prevent safe performance of the block
• Any coagulation abnormality which would be a contraindication for block placement
• Preoperative chronic renal dysfunction requiring renal replacement therapy or a serum creatinine greater than 1.4 mg/dL
• Body mass index >50
• Pregnancy
• Incarceration
• ASA classification greater than 3
• Inability to provide informed consent

• Participants must have had a histologic diagnosis of osteosarcoma at original diagnosis
• Disease Status: Patients with an isolated pulmonary recurrence of osteosarcoma can be enrolled on this study.
• Any history of metastatic disease at a site other than lung would make the patient ineligible for this study.
• The patient's treating team must consider the patient's disease to be resectable and the patient must be willing to undergo resection of all disease, including any lung lesion meeting criteria for likely metastatic disease, defined as: 3 or more lesions ≥ 3 mm in diameter OR a single lesion ≥ 5 mm.
• Patients with bilateral disease are eligible provided their disease is considered resectable. Resectable pulmonary nodules are defined as nodules that can be removed without performing a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels).
• Must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2, using the Karnofsky scale for patients > 16 years of age and the Lansky scale for patients ≤ 16 years of age
• Prior Therapy: Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to the start of protocol therapy.
• Participants must have normal organ and marrow function within 7 days of starting protocol therapy
• All participants and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent/assent document
• Additional criteria may apply
• Pregnancy or Breast Feeding
• Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as outlined in study protocol documentation
• Concomitant Medications: Patients receiving the following are not eligible:
• Corticosteroids or other immunosuppressive medications
• Patients who are currently receiving other investigational agents or other anti-cancer therapy
• Intercurrent Illnesses: Patients with uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements
• Autoimmune disorders: Patients with a history of any Grade autoimmune disorder are not eligible.
• Asymptomatic laboratory abnormalities (e.g., ANA, rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder.
• Patients with ≥ Grade 2 hypothyroidism due to history of autoimmunity are not eligible. Note: Hypothyroidism due to previous irradiation or thyroidectomy will not impact eligibility
• Allergies: Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Nivolumab (e.g., another humanized antibody) or Azacitidine are not eligible
• Safety and Monitoring: Patients who are considered unable to comply with the safety monitoring requirements of the study are not eligible
• Patients with known HIV or hepatitis B or C are excluded
• Patients who have received prior solid organ transplantation are not eligible
• Patients who have received prior anti-PD-1 directed therapy (mAb or small molecule) are not eligible

• Patients must be > 12 years and =< 39 years of age at the time of study enrollment
• Patients must have had histologic verification of osteosarcoma at original diagnosis or relapse
• Patients with diagnoses of osteosarcoma and confirmed HER2 expression of > 10% of osteosarcoma cells are eligible for the intervention
• Note: There is a mandatory tissue submission for HER2 staining during the Step 0 Eligibility Screening process. Metastatic tissue, when possible from the most recent relapse, is strongly preferred for HER2 staining over archival tissue from primary resection or diagnostic biopsy. The evaluation period for HER2 staining to determine eligibility for therapy will be less than 4 weeks from screening enrollment
• Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients with clinically inactive brain metastases may be included in the study. Patients with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Lastly, patient must have unresectable lesions or lesions with no intention to surgically remove in the 6 months following enrollment
• Patient's current disease state must be one for which they have received at least standard initial therapy, defined as systemic therapy combined with either radiation or surgery for local control of the primary tumor at diagnosis. Prior therapy after relapse is not required
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. Patients who are non-ambulatory as a result of prior surgical treatment for osteosarcoma should be considered ambulatory for the purposes of assessing performance status
• Patients must have recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. 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 anti-cancer 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 myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 4 weeks (28 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
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) 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
• 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: >= 30 days
• Vellular therapy: >= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 4 weeks (28 days) including palliative radiation therapy to the chest. >= 14 days after palliative local XRT to areas other than the chest or for whole brain radiotherapy
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, samarium): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior HER2 therapies including antibody drug conjugates (e.g. TDM-1 or DS-8201a), HER2 directed cellular therapies, HER2 receptor therapy (e.g. trastuzumab, pertuzumab) or small molecule antagonists of HER2 (e.g lapatinib or neratinib)
• Patients must be at least 7 days from the date of last surgery
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3, (granulocyte colony-stimulating factor [G-CSF] administration is not allowed within 1 week prior to Step 1 screening assessment) (for patients with solid tumors without known bone marrow involvement)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (for patients with solid tumors without known bone marrow involvement)
• Hemoglobin >= 8.0 g/dL at baseline (Red Blood Cell transfusion is not allowed within 1 week prior to screening assessment) (for patients with solid tumors without known bone marrow involvement)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 12 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
• For participants less than 18 years of age that screen fail only based on creatinine, a 24 hour urine collection may be used instead to confirm eligibility. A calculated GFR > 60 mL/min/1.73 m^2 using a 24 hour collection will meet criteria for inclusion on this trial
• Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age. For patients with documented Gilbert's syndrome (unconjugated hyperbilirubinemia) bilirubin must be < 3 x ULN for age (patients with solid tumors)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN. (if liver metastases present =< 5 x ULN). For the purpose of this study, the ULN for ALT is 45 U/L regardless of baseline and the ULN for AST is 50 U/L regardless of baseline (patients with solid tumors)
• Serum albumin >= 2.5 g/dL (patients with solid tumors)
• International normalized ratio (INR)/prothrombin time (PT) and either partial thromboplastin or activated partial thromboplastin time (aPTT) =< 1.5 x ULN (patients with solid tumors)
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before Step 1 enrollment
• Corrected QT interval (QTc) prolongation to < 470 ms (females) or < 450 ms (males) based on average triplicate 12-lead electrocardiogram (ECG)
• Pulse oximetry > 93% on room air
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) resulting from prior chemotherapy, surgery, and/or radiation must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
• All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• Pregnant, planning to become pregnant, or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug. Abstinence is an acceptable method of birth control
• Methods considered as highly effective methods of contraception include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral
• Intravaginal
• Transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
• Oral
• Injectable
• Implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner
• Complete sexual abstinence defined as refraining from heterosexual intercourse. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception
• Non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [< 147 pmol/L] is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method
• Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study
• Female subjects must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are receiving chloroquine or hydroxychloroquine within 14 days are not eligible for this trial
• Patients who have received a prior solid organ transplantation are not eligible
• Patients with a medical history of myocardial infarction within 180 days before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) or troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment are not eligible
• Patients who have a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART) are not eligible
• Patients who have spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms are not eligible
• Patients with a known history of severe hypersensitivity to DS-8201a or any excipient contained in the DS-8201a drug formulation are not eligible
• Patients who have an uncontrolled infection or non-healing surgical site are not eligible
• Patients with a known history of substance abuse or any other clinically significant medical conditions (i.e. psychological conditions) that may, in the opinion of the investigator, interfere with the patient's participation in the clinical study or evaluation of the clinical study results are not eligible
• Patients who have pulmonary compromise, ex hypoxia, resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.), or prior pneumonectomy are not eligible
• Patients who have a history of (non-infectious) ILD (interstitial lung disease)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening are not eligible
• Patients who have a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART) are not eligible. (Drainage and CART are not allowed within 2 weeks prior to screening assessment)
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible

• Diagnosed with RRMS per revised McDonald criteria (2017) with an EDSS score ≤ 6.5 at screening
• Neurologically stable with no evidence of relapse within the 28 days before signing the informed consent form (ICF)
• Either not currently receiving disease modifying MS therapy, or currently using fumarate drugs (dimethyl fumarate or diroximel fumarate)
• Patients must use a highly effective method of birth control or are sterile or postmenopausal as confirmed by study Investigator
• Patient has signed and understands the ICF
• Diagnosis of primary progressive MS or secondary progressive MS
• Uncontrolled or significant medical conditions (including active infection or chronic hepatitis) which, in the opinion of the Investigator, preclude participation
• Patients treated with glatiramer acetate, parenteral steroids or adrenocorticotropic hormone, β-interferon, plasma exchange, fingolimod, ozanimod, or siponimod within the 3 months prior to first dose
• Patients treated with cytotoxic agents (including, but not limited to, cladribine, mitoxantrone, cyclophosphamide, azathioprine, and methotrexate), laquinimod, teriflunomide, or IV gamma globulin within 12 months prior to first dose
• Patients treated with monoclonal antibody therapy (including natalizumab, daclizumab, rituximab, ofatumumab, and ocrelizumab) within 24 months prior to first dose
• Patients previously treated with alemtuzumab, total lymphoid irradiation, mesenchymal stem cell or hematopoietic stem cell transplantation, or tolerance-inducing therapies for MS
• Contraindication to or inability to undergo gadolinium-enhanced magnetic resonance imaging (MRI) scan
• Use of any investigational drug or experimental procedure within previous 6 months that would interfere with the assessment of ANK-700
• Patients who are pregnant or breastfeeding

• 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)

• 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.
• Patients ages 13
•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
• Subjects who had prior chemotherapy or radiotherapy before enrollment in the study.
• 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)

• Patient must be >=10 years of age at the time of signing the informed consent.
• Patient has a diagnosis of synovial sarcoma confirmed by histology.
• Patient has advanced (metastatic or unresectable) synovial sarcoma.
• In substudy 1, patient with metastatic synovial sarcoma who is newly diagnosed or previously untreated.
• In substudy 2, at the time of treatment, patient has received/completed treatment with anthracycline or anthracycline with ifosfamide for advanced (metastatic or inoperable) disease and progressed.
• Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.
• Patient must be positive for Human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated test in a designated central laboratory.
• Patients tumor has been pathologically reviewed by a designated central laboratory with confirmed positive NY-ESO-1 expression.
• Performance status: Eastern Cooperative Oncology Group of 0-1.
• Patient must have adequate organ function and blood cell counts 7 days prior to leukapheresis.
• Female patients of childbearing potential must have a negative urine or serum pregnancy test.
• Patient has measurable disease according to RECIST v1.1.
• Supportive radiotherapy has not affected >25 percent of bone marrow.
• In substudy 1, patient has been previously treated for metastatic synovial sarcoma.
• Central nervous system metastases.
• Any other prior malignancy that is not in complete remission.
• Previous treatment with genetically engineered NY-ESO-1-specific T cells.
• Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
• Prior gene therapy using an integrating vector.
• Previous allogeneic hematopoietic stem cell transplant.
• Clinically significant systemic illness: serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the Patient 's ability to tolerate protocol therapy or significantly increase the risk of complications, or, prior or active demyelinating disease.
• Patient has history of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
• Uncontrolled intercurrent illness.
• Current active liver or biliary disease.
• Pregnant or breastfeeding females (due to risk to fetus or newborn).
• Prior/concomitant therapy: any prior treatment-related toxicities must be Common terminology criteria for adverse events <=Grade 1 at the time of initiating study intervention (except for non-clinically significant toxicities).
• Other standard of care lines of therapy are allowed only if guidelines and washout periods are followed.
• Patient has active infection as defined in the protocol.
• Patient has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
• Patient had major surgery <=28 days of first dose of study intervention.