• 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

• Registered male or female primary Liver transplant candidate
• Age ≥18 years old
• Signed: 1) written informed consent document and 2) authorization to use and disclose protected health information
• Acute, fulminant liver failure
• Prior solid organ or bone marrow transplant
• Chronic use of hemodialysis or diagnosis of chronic renal failure, defined as chronic serum creatinine of >3 mg/dl for >2 weeks and/or requiring hemodialysis
• Multi-organ transplant
• Ventilator dependent
• Dependent on > 1 IV inotrope to maintain hemodynamics

• Patient must have a histologically confirmed diagnosis hepatocellular carcinoma; known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC will be excluded
• Locally advanced or metastatic disease
• Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
• Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).
• Child-Pugh Score A
• Age ≥ 18 years
• ECOG Performance score of 0-1
• Life expectancy greater than 6 months
• Following baseline laboratory values: 1. Total bilirubin ≤ 2.0 mg/ml 2. INR ≤ 1.7 3. Hgb ≥ 8.5 g/dl 4. AST, ALT ≤5 times ULN 5. Platelet count ≥ 50,000/mm3 6. Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min 7. Albumin ≥ 2.5 g/dl 8. Absolute neutrophil ≥ 1,500 cells/mm3
• Male and female subjects of child bearing potential must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
• Women of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study medication
• Subjects are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows: HBV-HCC: Controlled (treated) hepatitis B subjects will be allowed if they meet the following criteria: Antiviral therapy for HBV must be given for at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Subjects on active HBV therapy with viral loads under 100 IU/ml should stay on the same therapy throughout study treatment. Subjects who are anti-HBc (+), negative for HBsAg, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis. HCV-HCC: active or resolved HCV infection as evidenced by detectable HCV RNA or antibody. Patients who have failed HCV therapy as evidenced by detectable HCV RNA will be eligible. Subjects with chronic infection by HCV who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, subjects with successful HCV treatment are allowed as long as there are ≥4 weeks between completion of HCV therapy and start of study drug. Successful HCV treatment definition: SVR12.
•Prior therapy is allowed provided the following are met: at least 4 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation. Provided target lesion has increased in size by 25% or more or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible 1 week after treatment as long as the target lesion is not the treated lesion.
• Prior liver transplant;
• Patient who has received previous systemic therapy for HCC;
• Clinically significant, uncontrolled heart disease and/or recent events including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening;
• History of documented congestive heart failure (New York Heart Association functional classification III-IV);
• Documented cardiomyopathy;
• Patient has a left ventricular ejection fraction <40% as determined by MUGA scan or ECHO (MUGA and ECHO are not required prior to enrollment);
• Known human immunodeficiency virus (HIV) positive (testing not required);
• History of thromboembolic events (including both pulmonary embolism and deep venous thrombus but not including tumor thrombus) within the last 6 months;
• Hypersensitivity to IV contrast; not suitable for pre-medication;
• Active or fungal infections requiring systemic treatment within 7 days prior to screening;
• Known history of, or any evidence of, interstitial lung disease or active non-infectious pneumonitis;
• Evidence of poorly controlled hypertension which is defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management;
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication;
• Active, known, or suspected autoimmune disease with the following exceptions i) Subjects with vitiligo, type I diabetes mellitus, resolved childhood asthma or atopy are permitted to enroll; ii) Subjects with suspected autoimmune thyroid disorders may be enrolled if they are currently euthyroid or with residual hypothyroidism requiring only hormone replacement. iii) Subjects with psoriasis requiring systemic therapy must be excluded from enrollment
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the study or compromise compliance with the protocol (e.g. chronic pancreatitis, active untreated or uncontrolled fungal, bacterial, or viral infections, etc.);
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the study or compromise compliance with the protocol (e.g. chronic pancreatitis, active untreated or uncontrolled fungal, bacterial, or viral infections, etc.);
• Known history of active bacillus tuberculosis;
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of study administration. Inhaled or topical steroids and adrenal replacement doses >10 mg/day prednisone equivalents are permitted in the absence of autoimmune disease;
• Patient who has received radiotherapy ≤ 4 weeks prior to study entry. Palliative radiotherapy for symptomatic control is acceptable (if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned);
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery);
• Clinically apparent ascites on physical examination, ascites present on imaging studies is allowed;
• Patient has a known hypersensitivity to any of the excipients of bavituximab or pembrolizumab or monoclonal antibody;
• Active gastrointestinal bleeding within previous 2 months;
• History of any condition requiring anti-platelet therapy (aspirin >300 mg/day, clopidogrel >75 mg/day);
• Prisoners or subjects who are involuntarily incarcerated;
• Symptomatic or clinically active brain metastases;
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation, confirmed by a positive hCG laboratory test;
• Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agents;
• Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCV infection (anti-HCV Ab(+) and detectable HCV RNA) at study entry.

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

Key For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.

1. Age ≥ 18 2. Written and signed informed consent must be obtained 3. ECOG Performance Status 0 or 1 4. Weight ≥ 35 kg 5. Subjects must have histologically or cytologically, confirmed pancreatic adenocarcinoma: Cohort A: Subjects with previously untreated metastatic pancreatic adenocarcinoma (1st line metastatic disease) not previously treated with systemic therapies. Cohort B: Subjects with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin) 2nd line metastatic disease 6. Subjects must have at least 1 measurable lesion according to RECIST v1.1 7. All subjects must consent to providing archival tumor specimens 1. Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment. 2. Prior receipt of any immune-related therapy 3. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed 4. Subjects with a history of venous thrombosis within the past 3 months 5. Subjects with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 3 months prior to start of treatment 6. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment 7. Other invasive malignancy within 2 years. 8. Any history of leptomeningeal disease or cord compression. 9. Current or prior use of immunosuppressive medication within 14 days prior to the first dose

• A female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin (βhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
• A male subject with female partner(s) of childbearing potential:
• must agree to use contraception during the treatment period and for 6 months after the final study treatment administration.
• A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study treatment administration.
• Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
• Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
• Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
• Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
• Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
• Subject has ECOG performance status 0 or 1.
• Subject has predicted life expectancy ≥ 12 weeks.
• Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
• Hemoglobin (Hb) ≥ 9 g/dl. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL.
• Absolute Neutrophil Count (ANC) ≥ 1.5x10^9/L
• Platelets ≥ 100x10^9/L
• Albumin ≥ 2.5 g/dL
• Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or < 3.0 x ULN if liver metastases are present)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
• Estimated creatinine clearance ≥ 30 mL/min
• Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
• Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies as long as it was completed at least 6 months prior to randomization.
• Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
• Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to randomization.
• Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
• Subject has received other investigational agents or devices within 28 days prior to randomization.
• Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
• Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
• Subject has prior severe allergic reaction or intolerance to any component of CAPOX.
• Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
• Subject has significant gastric bleeding and/or untreated gastric ulcers that exclude the subject from participation.
• Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen (HBs Ag)) or C infection. NOTE: Screening for these infections should be conducted per local requirements.
• For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded.
• Subjects with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test are eligible.
• Subjects treated for HCV with undetectable viral load results are eligible.
• Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
• Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
• Subject has significant cardiovascular disease, including any of the following:
• Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident (CVA) or hypertensive crisis within 6 months prior to randomization.
• History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes
• QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects
• History or family history of congenital long QT syndrome
• Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible).
• Subject has a history of central nervous system (CNS) metastases and/or carcinomatous meningitis from gastric/GEJ cancer..
• Subject has known peripheral sensory neuropathy > grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
• Subject has had a major surgical procedure ≤ 28 days prior to randomization.
• Subject is without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
• Subject has psychiatric illness or social situations that would preclude study compliance.
• Subject has another malignancy for which treatment is required.
• Subject has any concurrent disease, infection, or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.

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

• Participants with a first diagnosis of HCC who have undergone either a curative resection or ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only) within 4-12 weeks prior to randomization
• Documented diagnosis of HCC that has been completely resected or ablated (RFA or MVA only)
• Absence of major macrovascular invasion (except Vp1/Vp2) and extrahepatic spread
• Absence of extrahepatic spread as confirmed by CT or MRI scan of the chest, abdomen, pelvis, and head prior to and following curative procedure
• Full recovery from surgical resection or ablation within 4 weeks prior to randomization
• High risk for HCC recurrence after resection or ablation
• For patients who received post-operative transarterial chemoembolization: full recovery from the procedure within 4 weeks prior to randomization
• For patients with resected HCC, availability of a representative baseline tumor tissue sample
• ECOG Performance Status of 0 or 1
• Child-Pugh Class A status
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Evidence of residual, recurrent, or metastatic disease at randomization
• Clinically significant ascites
• History of hepatic encephalopathy
• Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
• Have received more than 1 cycle of adjuvant TACE following surgical resection
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable arrhythmia, or unstable angina
• History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Active tuberculosis
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to Day 1 of Cycle 1.
• Co-infection with HBV and HCV
• Co-infection with HBV and hepatitis D viral infection
• Clinical significant uncontrolled or symptomatic hypercalcemia
• Any treatment for HCC prior to resection or ablation, including systemic therapy and locoregional therapy such as TACE
• Treatment with systemic immunostimulatory or immunosuppressive agents
• Inadequately controlled arterial hypertension
• History of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease
• Evidence of bleeding diathesis or significant coagulopathy
• Current or recent use of aspirin or full-dose oral or parenteral anticoagulants
• Core biopsy within 3 days of Day 1 of Cycle 1
• History of GI fistula, GI perforation, or intra-abdominal abscess
• Serious non-healing or dehiscing wound
• Major surgical procedure within four weeks
• Chronic daily treatment with a non-steroidal anti-inflammatory drug

• Men or women greater than or equal to 18 years old.
• Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing. Exclusion Criteria
• Active brain metastases from non-brain tumors.
• Myocardial infarction within 6 months of study day 1.
• Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Key
• Histologically-documented HPV-6- or HPV-11-positive respiratory papilloma or documentation of low-risk positive HPV using a Sponsor approved HPV-6/11 type-specific assay
• Requirement for frequent RRP intervention to remove or resect respiratory papilloma, as defined as at least two RRP surgical (including laser) interventions in the year prior to and including Day 0
• Must be an appropriate candidate for upcoming surgical intervention as per Investigator judgment and RRP Staging Assessment score
• Adequate bone marrow, hepatic, and renal function
• Participants must meet one of the below requirements:
• Be of non-child bearing potential (≥12 months of non-therapy-induced amenorrhea, confirmed by follicle-stimulating hormone [FSH], if not on hormone replacement)
• Be surgically sterile (vasectomy in males or absence of ovaries and/or uterus in females)
• Agree to use one highly effective or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and at least through week 12 after last dose
• Agree to abstinence from penile-vaginal intercourse, when this is the participant's preferred and usual lifestyle Key
• Recipient of therapy directed towards RRP disease (other than surgery or ablation) including but not limited to anti-virals (including cidofovir), radiation, chemotherapy, anti-angiogenic therapy (including bevacizumab), prophylactic HPV vaccination (including Gardasil) as therapeutic intervention, or therapy with an experimental agent within 3 months prior to Day 0
• Ongoing or recent (within 1 year) evidence of autoimmune disease that required treatment with systemic immunosuppressive treatments, with the exception of: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that requires only hormone replacement, or psoriasis that does not require systemic treatment
• Diagnosis of immunodeficiency or treatment with systemic immunosuppressive therapy within 28 days prior to the first dose of trial treatment, including systemic corticosteroids
• High risk of bleeding or require the use of anticoagulants for management of a known bleeding diathesis
• Recipient of any live virus vaccine within 4 weeks prior to the first dose of trial treatment or any non-live vaccine within two weeks prior to the first dose of trial treatment
• History of clinically significant, medically unstable disease which, in the judgment of the Investigator, would jeopardize the safety of the participant, interfere with trial assessment or evaluation, or otherwise impact the validity of the trial results
• Fewer than two acceptable sites are available for IM injection considering the deltoid and anterolateral quadriceps muscles. Study treatment should not be given within 2 centimeters (cm) of a tattoo, keloid or hypertrophic scar. If there is implanted metal, implanted device, within the same limb the use of the deltoid muscle on the same side of the body is excluded
• Prisoners or participants who are compulsory detained (involuntary incarceration) for treatment of either a psychiatric or physical (i.e. infectious disease) illness
• Any medical or psychological or non-medical condition that might interfere with the participation or safety of the participant, as determined by the investigator

1. At least 18 years of age. Both men and women and members of all races and ethnic groups will be included. 2. Willing and able to provide written informed consent 3. Pathologic diagnosis of rectal adenocarcinoma 4. T3-4 and/or N+ disease per AJCC 8th edition 5. No prior treatment for rectal adenocarcinoma 6. Eastern Cooperative Group (ECOG) performance status of 0-2. 7. Laboratory values supporting acceptable organ and marrow function within 30 days of eligibility confirmation. Defined as follows:
• WBC ≥ 3,000/mL;
• ANC WBC ≥ 1,000/mL;
• PLT ≥ 75,000/mL;
• T Bili ≤ 1.5 x upper limit of normal (ULN);
• AST/ALT ≤ 2.5 x ULN;
• Creatinine not above ULN, or creatinine clearance >50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal. 8. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting with the first dose of study therapy through 90 days after the last dose of study drugs. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). 1. Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT. 2. Prior RT to the pelvis. 3. Uncontrolled comorbid illness or condition including congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements. 4. Psychiatric illness/social situations that would limit consenting and compliance with study requirements. 5. Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants

• A male or female patient with a clinical diagnosis of BA
• Age at Kasai HPE ≤90 days
• Eligible to start study treatment within 3 weeks post-Kasai HPE Key
• Patients with intractable ascites
• Ileal resection surgery
• ALT ≥10× upper limit of normal (ULN) at screening
• Patients reliant only on total parenteral nutrition, or not able to take study medication orally, at randomization
• Acute ascending cholangitis (patients may be randomized after resolution of acute ascending cholangitis)
• Choledochal cystic disease
• INR >1.6 (the patient may be treated with Vitamin K intravenously; sample may be redrawn and if INR is ≤1.6 at resampling the patient may be randomized)
• Any other conditions or abnormalities, including congenital abnormalities, major cardiac surgery, hepatic, biliary, or GI disease which, in the opinion of the Investigator or Medical Monitor, may compromise the safety of the patient, the integrity of study results, or patient compliance with study requirements
• Weight <3.5kg at randomization

Selected 1. Age ≥ 18 years of age at the time of signing the informed consent. Patients > 70 years of age must have a G8 Health State Screening Tool (geriatric screening tool) score >. 2. Proficient mismatch repair/microsatellite stable (pMMR/MSS), histologically or cytologically-confirmed adenocarcinoma of the colon or rectum. Patients with any BRAF or KRAS mutation status are eligible. 3. Unresectable and measurable or evaluable disease per RECIST v1.1 4. ECOG performance status of 0 to 1 5. A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh biopsy) with an associated pathology report documenting pMMR/MSS mCRC must be confirmed to be available to send to the Sponsor for planned retrospective biomarker analyses. 6. Adequate organ function Selected 1. Prior systemic therapy for mCRC. Patients who received adjuvant/neoadjuvant therapy (ie, treatment with curative intent) for colorectal cancer are eligible if it has been ≥ 6 months between the last dose of systemic chemotherapy and the date of informed consent. 2. Any radiotherapy, chemotherapy, immunotherapy, biologic, investigational, or hormonal therapy for cancer treatment (except for adjuvant hormonal therapy for breast cancer or prostate cancer defined as M0 disease or PSA persistence/recurrence without metastatic disease) within 3 weeks prior to the first dose of trilaciclib/placebo. 3. Receipt of any low-dose systemic chemotherapeutic agent (e.g., low-dose methotrexate for rheumatoid arthritis) administered for a nononcologic purpose within 3 weeks prior to the first dose of trilaciclib/placebo. 4. Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids 5. QTcF interval > 450 msec (males) or > 470 msec (females) at screening. For patients with ventricular pacemakers, QTcF > 500 msec. 6. Personal or family history of long QT syndrome 7. Symptomatic peripheral neuropathy 8. History of interstitial lung disease (ILD) 9. Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation

• Males or females age of 18 to 75 years (inclusive)
• Definite or probable PBC diagnosis
• ALP ≥ 1.67x upper limit of normal (ULN)
• Total bilirubin (TB) ≤ 2x ULN
• UDCA for at least 12 months (stable dose ≥ 3 months) prior to screening, or unable to tolerate UDCA treatment (no UDCA for ≥ 3 months) prior to screening (per country standard-of-care dosing)
• Females participating in this study must be of non-child bearing potential or must be using highly efficient contraception for the full duration of the study and for 1 month after the last drug intake
• History or presence of other concomitant liver disease
• Clinically significant hepatic decompensation, including patients with cirrhosis/portal hypertension complications
• Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers
• Patient has a positive test for Human Immunodeficiency Virus (HIV)
• Evidence of any other unstable or untreated clinically significant disease
• History of alcohol abuse
• For female patients: known pregnancy or lactating
• Use of fibrates and glitazones within 2 months prior to screening
• Use of azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin) within 3 months prior to screening
• Use of antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines within 12 months prior to screening
• For patients with previous exposure to obeticholic acid (OCA), OCA should be discontinued 3 months prior to screening
• Patients who are currently participating in, plan to participate in, or have participated in an investigational drug study or medical device study containing active substance within 30 days or five half-lives, whichever is longer, prior to screening; for patients with previous exposure to seladelpar, seladelpar should be discontinued 3 months prior to screening.
• Patients with previous exposure to elafibranor
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5x ULN
• Albumin < 3.0 g/dL
• PBC Severely advanced patients according to Rotterdam criteria (TB > ULN and albumin < LLN)
• International normalized ratio (INR) > 1.3 due to altered hepatic function
• Creatine phosphokinase CPK > 2X ULN
• Serum creatinine > 1.5 mg/dL
• Significant renal disease

• 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

• Participants must have one of the following:
• Histologically documented muscle-invasive bladder carcinoma (MIBC) from transurethral resection of bladder tumor (TURBT) within 56 days prior to registration
• Histologically confirmed high grade upper tract urothelial carcinoma (UTUC) within 56 days prior to registration, with invasion confirmed by either a mass on cross-sectional imaging or a tumor directly visualized during upper urinary tract endoscopy within 56 days prior to registration
• Participants diagnosed with mixed urothelial carcinoma and variant histology within 56 days prior to registration may be eligible if the majority (> 50%) of the tumor consists of urothelial carcinoma. Participants with pure non-urothelial variant histologies or any small cell histology are not eligible
• Participants must have clinical stage T2-T4aN0M0 bladder or upper tract cancer confirmed by radiologic staging (computed tomography [CT] scan/magnetic resonance imaging [MRI] abdomen and pelvis, and CT scan/x-ray of the chest) within 56 days prior to registration
• Participants must have a bone scan within 56 days prior to registration if they have bone pain or elevated serum alkaline phosphatase
• Participants must have a bimanual examination under anesthesia within 56 days prior to registration
• Participants must not have received prior systemic chemotherapy, immunotherapy or radiotherapy for the treatment of muscle invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (UTUC). Other prior pelvic radiotherapy is allowed if it does not preclude surgery (radical cystectomy, nephroureterectomy or ureterectomy, based on location of primary tumor). Prior intravesical therapy is allowed
• Participants must not have received immunosuppressive medication within 14 days prior to registration, with the exception of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection) systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Participants must be >= 18 years of age
• Participants must have Zubrod performance status 0-2
• Participants must have history and physical examination within 28 days prior to registration
• Participants must be surgical candidates as deemed by the local site oncologic surgeon within 28 days prior to registration. This must be clearly documented
• Participants must have a serum creatinine =< the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 30 mL/min using the Crockroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
• Participants must be deemed cisplatin-ineligible based on greater than or equal to 1 of the following:
• Zubrod performance status = 2
• Creatinine clearance (calculated by Crockroft-Gault formula or measured) 30 to < 60 ml/min,
• Neuropathy > grade 1
• Hearing loss > grade 1
• Congestive heart failure > grade 2
• Hemoglobin >= 9.0 g/dL (within 28 days prior to registration)
• Absolute neutrophil count >= 1,500/mcL (within 28 days prior to registration)
• Platelets >= 100,000/mcL (within 28 days prior to registration)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to registration)
• Aspartate aminotransferase (AST) =< 2.5 x institutional ULN (within 28 days prior to registration)
• Alanine aminotransferase (ALT) =< 2.5 x institutional ULN (within 28 days prior to registration)
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and be class 2B or better
• Participants with known human immunodeficiency virus (HIV) must be on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration
• Participant must not have any other prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer Gleason score =< 3+4 in active surveillance, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
• Participants must not be pregnant or nursing due to the risk of harm to a fetus or nursing infant. Women/men of reproductive potential must have a negative serum or urine pregnancy test within 28 days prior to registration and must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• Participants must not have a history of active primary immunodeficiency
• Participants must not have a history of or active autoimmune or inflammatory disorder, with the exception of vitiligo, alopecia, hypothyroidism (stable on hormone replacement), or chronic skin condition that does not require systemic therapy

• 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.

• Patients in Group F must have a body surface area (BSA) >= 0.6 m^2
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients 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
• Patients must be newly diagnosed with histologically-proven primary pediatric hepatic malignancies including hepatoblastoma or hepatocellular carcinoma, except as noted below; patients with a diagnosis of hepatocellular neoplasm, not otherwise specified, should be classified and treated per hepatoblastoma treatment arms; note that rapid central pathology review is required in some cases; please note: all patients with histology as assessed by the institutional pathologist consistent with pure small cell undifferentiated (SCU) HB will be required to have testing for INI1/SMARCB1 by immunohistochemistry (IHC) according to the practices at the institution
• Patients with histology consistent with pure SCU must have positive INI1/SMARCB1 staining
• For all Group A patients, WDF status as determined by rapid review will be used to further stratify patients to Group A1 or A2
• For Groups B, C and D, rapid review is required if patients are either >= 8 years of age or have an alphafetoprotein (AFP) =< 100 at diagnosis
• For all Groups E and F patients, rapid central pathology review is required
• In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy
• Clinical situations in which emergent treatment may be indicated include, but are not limited to, the following circumstances:
• Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)
• Uncorrectable coagulopathy
• For a patient to maintain eligibility for AHEP1531 when emergent treatment is given, the following must occur:
• The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility criteria at the time of emergent treatment
• Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP1531 enrollment
• Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
• Patients may have had surgical resection of the hepatic malignancy prior to enrollment; all other anti-cancer therapy for the current liver lesion is prohibited
• 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: maximum serum creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 06 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 5 x upper limit of normal (ULN) for age
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 10 x upper limit of normal (ULN) for age
• Shortening fraction of >= 28% by echocardiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment) or
• Ejection fraction of >= 47% by echocardiogram or radionuclide angiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment)
• Group F patients only: QT/corrected QT (QTc) interval =< 450 milliseconds for males and =< 470 milliseconds for females (assessed within 8 weeks prior to study enrollment)
• Normal pulmonary function tests (including diffusion capacity of the lung for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen) (for patients receiving chemotherapy [Groups A, B, C, D, E2, F]); for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser); therefore, patients with a pre-disposition syndrome who have a prior malignancy are not eligible
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving other anticancer agents
• Patients with uncontrolled infection
• Patients who previously received a solid organ transplant, other than those who previously received an orthotopic liver transplantation (OLT) as primary treatment of their hepatocellular carcinoma
• Patients with hypersensitivity to any drugs on their expected treatment arm
• Group C: Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
• Group D:
• Patients with chronic inflammatory bowel disease and/or bowel obstruction
• Patients with concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
• Group F:
• Patients with peripheral sensitive neuropathy with functional impairment
• Patients with a personal or family history of congenital long QT syndrome
• These criteria apply ONLY to patients who may receive chemotherapy (all groups other than Group E1):
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• Note for Group F: patients of childbearing potential should use effective birth control during treatment with sorafenib and for at least 2 weeks after stopping treatment

1. Signed written informed consent granted prior to initiation of any study-specific procedures 2. 18 years of age or older 3. Histologically or cytologically confirmed locally advanced, inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), or metastatic iCCA or mixed histology tumors (combined hepatocellular-cholangiocarcinoma [cHCC-CCA]) 4. Substudy 1: FGFR2 fusion status based on the following assessments: a) If central laboratory designated by Sponsor: Positive FISH test; and/or b) If non-central laboratory: i) Positive FISH or NGS test: patients may be enrolled and may start dosing, but central confirmation is required* ii) Negative FISH or NGS test: tissue may be submitted to the central laboratory designated by the Sponsor, and patients may only be enrolled if the central test is positive *Using standard protocols and approved by local IRB/EC, by CLIA or other similar agency. Substudy 2: FGFR2 mutation/amplification status based on local NGS testing performed or commissioned by the respective study site. 5. Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression 6. Measurable disease by RECIST version 1.1 criteria 7. ECOG performance status ≤ 1 8. Adequate organ functions as indicated by the following laboratory values (based on screening visit values from the central laboratory).
• Hematological
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Platelet count ≥ 75 x 109/L
• International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤ 3 for subjects receiving anticoagulant therapy such as Coumadin or heparin
• Hepatic
• Total bilirubin ≤ 2 x ULN
• AST and ALT ≤ 3 ULN (≤ 5 x ULN for subjects with liver metastases)
• Albumin ≥ 2.8 g/dL
• Renal
• Serum creatinine ≤ 1.5 x ULN
• Creatinine clearance of ≥ 30 mL/min as estimated by the Cockcroft-Gault equation 9. Female and male patients of child-producing potential must agree to avoid becoming pregnant or impregnating a partner, respectively, use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse, during the study*, and until at least 120 for 90 days after the last dose of derazantinib. *From the day of first study medication, or for oral contraception from 14 days before first study medication. Male patients are considered not to be of child-producing potential if they have azoospermia (whether due to vasectomy or an underlying medical condition). Female patients are considered not to be of child-producing potential if they are:
• postmenopausal* , or
• have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening, or
• have a congenital or acquired condition that prevents childbearing. Male or female patients of child-producing potential must agree to comply with one of the following until at least 120 days after the last dose of derazantinib: 1. Abstinence from heterosexual activity** 2. Using (or having their partner use) an acceptable method of contraception during heterosexual activity. Acceptable methods of contraception are***:
• any ONE of:
•an intrauterine device (IUD)
•vasectomy of a female patient's male partner
•a contraceptive rod implanted into the skin.
• any TWO in combination of:
•diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide)
•cervical cap with spermicide (nulliparous women only)
•contraceptive sponge (nulliparous women only)
•male condom or female condom (cannot be used together)
•hormonal contraceptive (oral contraceptive pill [estrogen/progestin pill or progestin-only pill], contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection) *Postmenopausal is defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post -menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is not sufficient.
• Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.
• If a contraceptive method listed above is restricted by local regulations/guidelines, then it does not qualify as an acceptable method of contraception for subjects participating at sites in this country/region. 1. Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:
• One chemotherapy or biological (e.g., antibody) cycle interval
• Five half-lives of any small-molecule investigational or licensed medicinal product
• Two weeks, for any investigational medicinal product with an unknown half-life
• Four weeks of curative radiotherapy
• Seven days of palliative radiotherapy
• 28 days of radiotherapy 2. Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of derazantinib 3. Previous treatment with any FGFR inhibitor (e.g., Balversa® [erdafitinib], Pemazyre® [pemigatinib], infigratinib, rogaratinib, futibatinib, lenvatinib, ponatinib, dovitinib, nintedanib, AZD4547, LY2784455).
•Subjects who received less than four weeks of therapy and were unable to continue therapy due to toxicity will be allowed to participate 4. Unable or unwilling to swallow the complete daily dose of derazantinib capsules 5. Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications) 6. Current evidence of clinically significant corneal or retinal disorder likely to increase the risk of eye toxicity, including but not limited to bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination. 7. Concurrent uncontrolled or active hepatobiliary disorders, untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, biloma or abscess (to be eligible, the subjects have to be treated and disorders/complications should be resolved within 2 weeks prior to the first dose of derazantinib) 8. History of significant cardiac disorders:
• Myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of derazantinib (MI that occurred > 6 months prior to the first dose of derazantinib will be permitted)
• QTcF >450 msec (males or females) 9. Serum electrolyte abnormalities defined as follows:
•Hyperphosphataemia: Serum phosphate > institutional ULN
•Hyperkalemia: > 6.0 mmol/L
•Hypokalemia: < 3.0 mmol/L
•Hypercalcemia: corrected serum calcium < 1.75 mmol/L (< 7.0 mg/dL)
• Hypocalcemia: corrected serum calcium > 3.1 mmol/L (> 12.5 mg/dL)
• Hypomagnesemia: < 0.4 mmol/L (< 0.9 mg/dL) 10. Significant gastrointestinal disorder(s) that could, in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of derazantinib (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection) 11. History of additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer. 12. Concurrent uncontrolled illness not related to cancer, including but not limited to:
• Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
• Known uncontrolled human immunodeficiency virus (HIV) infection
• Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration 13. Blood or albumin transfusion within 5 days of the blood draw being used to confirm eligibility 14. Pregnant or breast feeding 15. Known hypsersensitivity to derazantinib, or to any of the study drug excipients (starch, lactose, crospovidone, magnesium stearate)

1. ≥ 18 years old 2. Signed and dated written informed consent 3. Histologically or cytologically confirmed unresectable locally advanced or metastatic hepatocellular carcinoma. Measurable or evaluable disease by RECIST 1.1 criteria. Patients can be either untreated or have progressed on both bevacizumab and atezolizumab. 4. Child-Pugh Class A. 5. ECOG performance status ≤ 1 (see Appendix A) and life expectancy ≥ 3 months. 6. Body weight > 30 kg. 7. Measured creatinine clearance (crCL) >40 mL/min or calculated crCL >40 mL/min as determined by Cockcroft-Gault (using actual body weight). 8. Sexually active pre-menopausal female subjects (and female partners of male subjects) must use highly effective contraceptive measures, while on study and for at least 90 days after the last dose of study drug. Sexually active male subjects must use adequate contraceptive measures, while on study and for at least 90 days after the last dose of study drug. All fertile male and female subjects and their partners must agree to use a highly effective method of contraception. 1. Subjects who have received prior systemic treatment for HCC except for both bevacizumab and atezolizumab. 2. Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of study drug. 3. Brain metastases or spinal cord compression. Subjects with suspected brain metastases at screening should have an MRI (preferred) or CT scan each preferable with IV contrast of the brain prior to study entry. Brain metastases will not be recorded on RECIST Target Lesions at baseline. 4. Any of the following hematologic abnormalities:
• Hemoglobin < 9.0 g/dL
• Absolute neutrophil count (ANC) < 1500 per mm3
• Platelet count < 75,000 per mm3 5. Any of the following serum chemistry or urinalysis abnormalities:
• Total bilirubin > 2 × ULN (>2.5 mg/dL in subjects with Gilbert's syndrome)
• AST or ALT > 5 × ULN
• Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN for subjects with liver or bone metastasis)
• Serum creatinine > 1.5 × ULN •> 2+ proteinuria 6. History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy (eg, no lactulose, rifaximin, etc if used for purposes of hepatic encephalopathy). 7. GI Bleeding (eg, esophageal varices or ulcer bleeding) within 12 months. (Note: For patients with a history of GI bleeding for more than 12 months or assessed as high risk for esophageal variceal bleed by the Investigator, adequate endoscopic therapy according to institutional standards is required). 8. Clinically meaningful ascites defined as ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. Subjects on stable doses of diuretics for ascites for ≥ 2 months are eligible. 9. Main portal vein thrombosis (Vp4) as documented on imaging. (VP4 is defined as portal vein thrombosis in the main trunk of the portal vein or a portal vein branch contralateral to the primarily involved lobe (or both). 10. For subjects who require ongoing therapeutic anti-coagulation or anti-platelet therapy; the subject must be off either therapy for at least 7 days prior to the first dose of investigational product. Low-dose aspirin for cardiac prophylaxis/protection is permitted per local institutional standards. 11. Patients co-infected with HBV and HCVHBV positive [presence of hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥10IU/ml)]; HCV positive (presence of anti-HCV antibodies). 12. Major surgery (as defined by the investigator) within 28 days prior to first dose of IP or still recovering from prior surgery. Local procedures (eg, core needle biopsy, and prostate biopsy) are allowed if completed at least 3 days prior to the administration of the first dose of study treatment. 13. Significant cardiovascular disease, including:
• Clinically symptomatic heart failure. Subjects with a history of heart failure must have an ECHO or MUGA scan to document left ventricular ejection fraction (LVEF) > 45% prior to start of protocol therapy
• Any New York Heart Association classification ≥ Class 2 (prefer Class 0 or 1)
• Any stenting procedure within the last 3 months
• Venous thromboembolism or arterial thromboembolism within the last 3 months
• Any IVC tumor thrombosis
• History of a hemorrhagic event (i.e., GI bleed within 6 months)
• Uncontrolled hypertension: blood pressure >150/95 mmHg on more than 2 antihypertensive medications, on two consecutive measurements obtained at least 24 hours apart. Subjects with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 2 weeks prior to start of protocol therapy.
• Myocardial infarction within 3 months prior to start of protocol therapy 14. Subjects with delayed healing of wounds, ulcers, and/or bone fractures 15. Serious/active infection or infection requiring parenteral antibiotics 16. Inadequate recovery from any prior surgical procedure; major surgical procedure within 4 weeks prior to start of protocol therapy. 17. Inability to comply with protocol requirements 18. History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study drug and low potential risk for recurrence
• Adequately treated non-melanoma skin cancer of lentigo maligna without evidence of disease 19. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 20. Patients with a history or current HBV infection (detectable HBV DNA), should be placed on anti-viral treatment and tested at every cycle for HBV DNA viral load. 21. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study intervention. 22. Treatment with systemic hormonal therapy within 3 weeks prior to start of protocol therapy, with the exception of:
• Hormonal therapy for appetite stimulation or contraception
• Nasal, ophthalmic, inhaled and topical steroid preparations
• Oral replacement therapy for adrenal insufficiency
• Low-dose maintenance steroid therapy (equivalent of prednisone 10mg/day) for other conditions
• Hormone replacement therapy such as testosterone 23. Strong CYP3A4 inducers (see Appendix B) within 2 weeks prior to start of, or during, protocol therapy. 24. Prior exposure to tivozanib or durvalumab. For subjects who have received prior atezolizumab:
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• Must not have experienced a Grade ≥ 3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy. Note: Participants with an endocrine AE of Grade ≤ 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day. 25. History of allogeneic organ transplantation 26. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Subjects without active disease in the last 5 years may be included but only after consultation with Medical Monitor
• Subjects with celiac disease controlled by diet alone 27. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent 28. History of leptomeningeal carcinomatosis 29. History of active primary immunodeficiency 30. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) 31. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients 32. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or during the follow-up period of an interventional study 33. Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug. Note: Subjects, if enrolled, should not receive live vaccine whilst receiving study drug and up to 30 days after the last dose of study drug. 34. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 35. Previous study drug assignment in the present study.

1. Diagnosis of WD by Leipzig Criteria > 4. 2. Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year prior to screening. 3. Body mass index < 30 kilograms/meter squared. 4. Able to cooperate with a percutaneous liver biopsy. 5. Willing and able to follow protocol-specified contraception requirements. 6. Capable of giving signed informed consent. 1. Decompensated cirrhosis or Model for End Stage Liver Disease score > 13. 2. Modified Nazer score > 7. 3. Clinically significant gastrointestinal bleed within past 3 months. 4. Alanine aminotransferase > 2 × upper limit of normal. 5. History of bleeding abnormality or known coagulopathy, including platelet count < 100,000, and international normalized ratio for prothrombin time ≥ 1.5. 6. Participant unwilling to accept blood products, if required. 7. Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care. 8. Hemoglobin less than lower limit of the reference range for age and sex. 9. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease 5) or creatinine clearance < 30 milliliters/minute. 10. Lymphoma, leukemia, or any malignancy within the past 5 years. 11. Current or chronic history of liver disease not associated with WD.

• STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
• STEP 1 REGISTRATION: Participants must have primary tumor in place
• STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:
• Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast Scans must be performed within the following timeframes:
• Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
• Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment
• STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
• STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
• STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
• STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
• STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
• STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
• CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2 • STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
• Stable disease
• Partial response
• The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1
• STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
• STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
• STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
• 2 infusions of nivolumab + 1 infusion of ipilimumab
• 2 infusions of pembrolizumab
• 2 infusions of avelumab
• STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
• STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
• STEP 2 REGISTRATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• STEP 2 REGISTRATION: Serum creatinine =< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)
• STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
• STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:
• Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
• Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:
• Treatment naive participants must not have received any pre-randomization treatment.
• Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:
• 4 infusions of nivolumab
• 4 infusions of ipilimumab
• 4 infusions of pembrolizumab
• 7 infusions of avelumab
• STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:
• Treatment naive participants must not have received any immunotherapy within a year of registration
• Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
• STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
• STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
• STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
• STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
• STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years

Key
• A documented diagnosis of eosinophilic esophagitis (EoE)
• Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration Key
• Body weight <5 kg or ≥60 kg at screening
• Other causes of esophageal eosinophilia
• Active Helicobacter pylori
• History of Crohn's disease, ulcerative colitis, celiac disease, or prior esophageal surgery
• Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening
• Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline standard of care endoscopy
• History of bleeding disorders or esophageal varices that, in the opinion of the investigator, would put the patient at undue risk for significant complications from an endoscopy procedure
• Active parasitic infection or suspected parasitic infection
• Known or suspected immunodeficiency disorder NOTE: Other protocol defined inclusion/exclusion criteria apply.

Key
• Patients with histologically documented gastric or gastroesophageal junction adenocarcinoma with resectable disease (Stage II or higher per AJCC 8th edition).
• Patients must undergo radical surgery.
• No prior anti-cancer therapy for the current malignancy.
• World Health Organization (WHO)/ECOG performance status of 0 or 1 at enrollment.
• Adequate organ and marrow function.
• Availability of tumor sample prior to study entry.
• Must have a life expectancy of at least 24 weeks. Key
• Patients with peritoneal dissemination or distant metastasis.
• Patients with adenosquamous cell carcinoma, squamous cell carcinoma, or GI stromal tumor.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
• Contra-indication to any of the study drugs.
• History of allogeneic organ transplantation.

• Diagnosis of Down syndrome
• Age 10-21 years
• Prior adenotonsillectomy
• Severe OSA (AHI > 10, AHI < 50, no more than 25% AHI attributable to central events) based on prior in-lab PSG performed after adenotonsillectomy and within 18 months of enrollment
• Approval from at least two of the three physician reviewers based upon the results of a routine drug-induced sleep endoscopy (DISE) having occurred within 12 months of enrollment
• Subjects must have either tracheotomy or be ineffectively treated with CPAP due to non-compliance, discomfort, un-desirable side effects, persistent symptoms despite compliance use, or refusal to use the device
• Children and their parents/guardians must be willing to have stimulation hardware permanently implanted, and be willing to participate in follow-up visits, postoperative PSG, and questionnaire completion
• Children's parents/guardians must complete a questionnaire confirming that their child is capable of communicating feelings of pain or discomfort. They must also confirm they are able to assess their child for adverse effects related to device implantation
• Children and their parents/guardians must be proficient in English
• Body mass index (BMI) above the 95th percentile for subject's age
• Circumferential airway collapse at the level of the velopharynx observed during DISE
• Other medical conditions resulting in medical instability (eg. congestive heart failure, recent open heart surgery, immunosuppression, or chronic lung disease or aspiration)
• Presence of another medical condition requiring future magnetic resonance imaging (MRI) of the chest
• Patients with another implantable device which could interact unintentionally with the Inspire system
• Any contraindication for general anesthesia
• History of bleeding or clotting disorders and those on blood thinning or NSAID medications for the week prior to implantation surgery. Subjects will be asked to refrain from the use of NSAIDS for two weeks after implantation or any revision surgeries
• Subject is currently taking muscle relaxant medication
• Life expectancy less than 12 months
• Subject's inability to communicate pain or discomfort to their caretaker/parent, based on parental or investigator assessment
• Nonverbal candidates will be excluded due to an inability to complete testing procedures including expressive language sampling
• Subjects with a co-occurring diagnosis of autism spectrum disorder
• Subjects that have a positive β-HCG
• Subjects deemed unfit for participation by the investigator for any other reason

1. Women age 21 or older 2. Prior total hysterectomy (no cervix present) 3. Prolapse beyond the hymen (defined as Ba, C, or Bp > 0 cm) 4. Vaginal cuff descent into at least the lower two thirds of the vagina (defined as point C> -2/3 TVL) 5. Bothersome bulge symptoms as indicated on question 3 of the PFDI-20 form relating to 'sensation of bulging' or 'something falling out' 6. Desires surgical treatment for post-hysterectomy vaginal prolapse 7. Available for up to 60 month follow-up 1. Previous synthetic material or biologic grafts (placed vaginally or abdominally) to augment POP repair including anterior, posterior and/or apical compartments 2. Known previous formal SSLS performed for either uterovaginal or post-hysterectomy vaginal vault prolapse * 3. Known adverse reaction to synthetic mesh or biological grafts; these complications include but are not limited to erosion, fistula, or abscess 4. Unresolved chronic pelvic pain-active 5. Prior abdominal or pelvic radiation 6. Contraindication to any of the index surgical procedures
• Known Horseshoe Kidney or Pelvic Mass overlying the sacrum
• Active diverticular abscess or active diverticulitis
• Shortened vaginal length (<6 cm TVL)
• NOTE:
• Only documented SSLS will be an exclusion.
• Mesh used for only mid-urethral sling will NOT be an exclusion
• If prior POP repair is unknown and unable to be documented, subjects will be eligible based on clinician judgment. The investigator will examine and assess for evidence of mesh or graft if no evidence of mesh or graft is present on examination subject remains eligible.

Part 1 Open-Label Extension:
• Patients previously enrolled in etrolizumab Phase III study GA29144 (NCT02394028) who meet the eligibility criteria for open-label etrolizumab as described in the protocol Part 2 Safety Monitoring:
• Patients who participated in etrolizumab Phase III study GA29144 (NCT02394028) and are not eligible or choose not to enter Part 1
• Patients who transfer from Part 1
• Completion of the 12-week safety follow-up period prior to entering Part 1 Open-Label Extension:
• Any new, significant, uncontrolled condition Part 2 Safety Monitoring:
• No exclusion criteria

• Subjects aged 1 to 16 years who in the judgment of the investigator are candidates for gastric acid suppression therapy (ie, those with a presumptive diagnosis of GERD, a clinical diagnosis of suspected GERD, symptomatic GERD, or endoscopically proven GERD) and whom the investigator judges would need to receive IV PPI therapy for at least 4 days.
• Body weight > 5th percentile for age.
• Y-site or dedicated IV line for administration of pantoprazole sodium.
• Expected survival for at least 30 days.
• Fertile male and female subjects of childbearing potential at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. Female subjects of non-childbearing potential must be premenarchal, have undergone hysterectomy with bilateral oophorectomy, have medically confirmed ovarian failure, or achieved post-menopausal status.
• Participation in other studies involving investigational drug(s) or treatment with an investigational drug within 30 days or 5 half lives prior to study entry and/or during study participation.
• Other severe acute or chronic medical or psychiatric condition or laboratory 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 subject inappropriate for entry into this study.
• Pregnant females; breastfeeding females; fertile male subjects, and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception for the duration of the study and for at least 28 days after last dose of investigational product.
• Serum CK levels >3x ULN.
• Known history of HIV or clinical manifestations of AIDS.
• Known hypersensitivity to PPIs or to any substituted benzimidazole or to any of the excipients.
• History of treatment with any PPI within 2 days (48 hours) before investigational product dosing on Day 1.
• Use of H2RAs, sucralfate, misoprostol, or prokinetic agents, and bismuth preparations within 1 day (24 hours) before investigational product dosing on Day 1.
• Any disorder requiring chronic (every day) use of warfarin, carbamazepine, or phenytoin, methotrexate, atazanavir or nelfinavir, clopidogrel, and potent inhibitors and inducers of CYP2C19.
• Chronic (daily) use of glucocorticoids. Steroid inhalers and topical steroids may be used.
• Active malignancy of any type, or history of a malignancy (Subject with a history of malignancies that have been surgically removed or eradicated by irradiation or chemotherapy and who have no evidence of recurrence for at least 5 years before Screening are acceptable).
• ALT or BUN >2.0 ULN or estimated creatinine >1.5 X ULN for age or any other laboratory abnormality considered by the Investigator to be clinically significant within 14 days before Screening.
• In the Investigator's opinion, a chronic condition (eg, diabetes, epilepsy), which is either not stable or well controlled and may interfere with the conduct of the study.
• History of sensitivity to heparin or heparin induced thrombocytopenia.