• 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

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.

• 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.

• Type 2 Diabetes Mellitus
• Echocardiographic demonstration of diabetic cardiomyopathy
• Peak VO2 < 75% of predicted normal value based on age and gender
• Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart failure
• Prior echocardiogrphic measurement of ejection fraction (EF) < 40%
• Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), coronary artery disease (CAD) or stroke
• Severe or moderate cardiac valve disease requiring intervention
• Clinically significant arrhythmia
• Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or hypertrophic cardiomyopathy
• Blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening
• HbA1c >8.5% at screening
• Severe disease that would impact the performance of a cardio-pulmonary exercise test

• 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.

• Treated or untreated stage I hypertension
• Diabetes mellitus,
• Renal impairment (serum creatinine > 1.4 mg/dL),
• Any heart diseases such as congestive heart failure, sustained arrhythmia, or coronary heart disease,
• Chronic regular NSAID use,
• Allergy to thiazide diuretics,
• Gastro-esophageal reflux disease (GERD) requiring treatment with acid reducing agents or antacid more than once a week,
• Esophageal-gastric ulcer or history of gastrointestinal bleeding,
• Chronic diarrhea, vomiting,
• Excessive sweating,
• Unprovoked hypokalemia (serum K < 3.5 mmol/L) or hyperkalemia (serum K > 5.3 mmol/L),
• Abnormal liver function test (Aspartate transaminase (AST) or Alanine transaminase (ALT) above upper limit of normal range),
• Subjects on any potassium supplement on a regular basis for any reason, such as patients with primary aldosteronism,
• Pregnancy,
• History of major depression, bipolar disorder, or schizophrenia,
• History of substance abuse,
• Gout,
• Metabolic alkalosis, with serum bicarbonate > 32 meq/L,
• Severe dietary salt restriction, less than1/2 spoonful or 50 meq sodium/day.
• Patient with Claustrophobia will not have MRI but can still participate in the study without MRI
• Metal implants will not have MRI but can still participate in the study without MRI

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

• Male or female, age equal to or above 50 years at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus
• HbA1c 6.5%
•10.0% (47
•86 mmol/mol) (both inclusive) (latest available and no more than 30 days old local laboratory assessment based on medical records or point of care measurement)
• At least one of the below conditions (a-d): a) Coronary heart disease defined as at least one of the following: i. Prior myocardial infarction ii. Prior coronary revascularisation procedure iii. 50% or above stenosis in coronary artery documented by cardiac catheterisation, computerized tomography coronary angiography iv. Coronary heart disease with ischaemia documented by stress test with any imaging modality b) Cerebrovascular disease defined as at least one of the following: i. Prior stroke ii. Prior carotid artery revascularisation procedure iii.50% or above stenosis in carotid artery documented by X-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an Ankle-brachial index (ABI) below 0.85 at rest ii. Intermittent claudication with a 50% or above stenosis in peripheral artery (excluding carotid) documented by X-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound iii. Prior peripheral artery (excluding carotid) revascularization procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or osteomyelitis) d) Chronic kidney disease defined as: i. eGFR below 60 mL/min/1.73 m^2 (based on medical records using latest available and no more than 6 months old assessment)
• Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
• Heart failure presently classified as being in New York Heart Association Class IV
• Treatment with any glucagon-like peptide-1 receptor agonist within 30 days before screening

• Male or female, age above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening.
• HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive).
• BMI equal to or above 25 kg/m^2
• Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens:
• No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *:
• Metformin (equal to or above1500 mg or maximum tolerated or effective dose).
• Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose).
• Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose).
• Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label).
• Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out).
• Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed.
• Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

• Signing of the trial specific informed consent
• Completion of the treatment period and Visit 7 assessments of trial TCH-306, including collection and upload of Visit 7 DXA scan
• Fundoscopy at Visit 7 in trial TCH-306 without signs/symptoms of intracranial hypertension or diabetic retinopathy stage 2 / moderate or above
• Diabetes mellitus if any of the following are met: 1. Poorly controlled diabetes, defined as HbA1C higher than 7.5% according to central laboratory at Visit 6 in trial TCH-306 2. Use of diabetes mellitus drugs other than metformin and/or dipeptidyl peptidase-4 (DPP-4) inhibitors
• Active malignant disease or history of malignancy. Exceptions are: 1. Resection of in situ carcinoma of the cervix uteri 2. Complete eradication of squamous cell or basal cell carcinoma of the skin
• Known history of hypersensitivity and/or idiosyncrasy to the investigational product (somatropin or excipients)
• Female who is pregnant, plans to become pregnant, or is breastfeeding
• Female participant of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) not willing throughout the trial to use contraceptives as required by local law or practice. Details included in Appendix 4/section 10.4 of the protocol
• Male participant not willing throughout the trial to use contraceptives as required by local law or practice. Details included in Appendix 4/ section 10.4 of the protocol
• Any disease or condition that, in the judgement of the investigator, may make the participant unlikely to comply with the requirements of the protocol or any condition that presents undue risk from the investigational product or trial procedures

• Male or female and age above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
• HbA1c of 7.0
•10.0% (53.0
•85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
• Insulin naïve. The following exceptions are permitted: short term insulin treatment for a maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes.
• Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes for 90 days or more before screening. The treatment can be with or without any of the following anti diabetic drugs with stable doses for 90 days or more before screening: Metformin
•Sulfonylureas (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation)
•Meglitinides (glinides)(Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation)
•DPP 4 inhibitors (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation)
•Sodium glucose co transporter 2 inhibitors
•Alpha-glucosidase inhibitors - Thiazolidinediones
•Marketed oral combination products only including the products listed above.
• Body mass index (BMI) below or equal to 40.0 kg/m^2.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
• Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or systemic corticosteroids).
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
• Any episodes (as declared by the participant or in the medical records) of diabetic ketoacidosis within 90 days before screening.
• Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
• Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
• Chronic heart failure classified as being in New York Heart Association Class IV at screening.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil dilation is a requirement unless using a digital fundus photography camera specified for non dilated examination

1. Pre-pubescent girls (age 2 years [12 kg minimum] to 8 years inclusive; skeletal age <10 years) or boys (age 2 years [12 kg] to 9 years inclusive; skeletal age <11 years). 2. Confirmed classic 21-hydroxylase deficiency evident by genotype groups A, A1 or B or clinical course (e.g., adrenal crisis with documented hyperkalemia and hyponatremia, at diagnosis or during a later evaluation; ambiguous genitalia in females). Documentation of one or both parents' genotypes may be required to confirm the subject's genotype. 3. Requirement for standard of care fludrocortisone (any dose) and ≥10 mg/m2/day of hydrocortisone for at least 1 month prior to the study consent. 4. Morning serum androstenedione concentrations >1.5 x Upper limit normal (ULN) after 7 days of dosing with doses of hydrocortisone required for physiologic replacement. 5. At least one parent (or other legally acceptable representative) must sign the informed consent form before the performance of any study procedures, but both parents must sign if both have parental rights. Children who are capable of providing assent (typically 10 years of age and older) must sign an assent form before the performance of any study procedures 1. Evidence of central puberty: Tanner Stage >2 for breast development in girls or testicular volume >4 mL in boys, or random luteinizing hormone (LH) >0.3 milli-international units (mIU)/mL. Subjects with pubic and/or axillary hair as the only sign of puberty onset will be allowed. 2. Current or history of hepatitis from any etiology, including history of active viral hepatitis A, B, or C. 3. Patients with baseline hepatic impairment are excluded from this trial. To be eligible for this protocol, patients must meet all of the following criteria: AST, ALT and Total bilirubin < ULN Albumin > lower limits of normal (LLN) No evidence of ascites No evidence of encephalopathy 4. Abnormalities of liver function developing during the study 5. Abnormal renal function tests, defined as blood urea nitrogen (BUN) or creatinine >1.5 ULN for age. 6. Significant anemia (hemoglobin < 12 g/dl). If documented to be due to iron deficiency, subjects may be rescreened 3 months after this has been treated. 7. Clinically significant abnormality in the 12-lead electrocardiogram (ECG) 8. A history of a malabsorption syndrome. 9. Evidence of active malignancy. 10. Serious or uncontrolled co-existent disease, including active or uncontrolled infection. Subjects may be rescreened after resolution of any such condition. 11. Concurrent medical condition or disease other than 21-hydroxylase deficiency that may interfere with linear growth or that requires concomitant therapy that is likely to interfere with study procedures or results. 12. Asthma or other condition requiring treatment with systemic corticosteroids within the past 3 months. Asthma treatment with inhaled corticosteroids is permitted. 13. Treatment with potentially hepatotoxic medications (statins); strong inhibitors of CYP3A4 (ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), or CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). CYP2C8 substrates (rosiglitazone, pioglitazone, rapaglinide) and CYP2D6 substrates (dextromethorphan, thioridazine) should be avoided 14. Treatment with medications to affect puberty or synthesis of sex steroids, including gonadotropin releasing hormone agonists, aromatase inhibitors, or androgen receptor blockers (e.g., flutamide, spironolactone). However, a gonadotropin releasing hormone agonist may be started during the study for treatment-emergent central puberty without disqualifying the subject 15. Treatment with growth hormone at enrollment or during the course of the study. 16. Known allergies, hypersensitivity, or intolerance to abiraterone acetate or its excipients (refer to United States Prescribing Information). 17. Has received an investigational drug within 4 weeks of the planned first dose of study drug or is currently enrolled in an investigational interventional study. 18. Any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments. 19. Presence or history of cataracts.

• Male or female, age greater than or equal to 18 years at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus greater than or equal to 10 years prior to the day of screening
• HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive)
• Eye inclusion criteria (both eyes must meet all criteria):
• Early Treatment Diabetic Retinopathy Study (ETDRS) level of 10-75 (both inclusive) evaluated by fundus photography and confirmed by central reading centre
• No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema twelve months prior to the day of screening
• No anticipated need for ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema within six months after randomisation
• Best-corrected visual acuity greater than or equal to 30 letters using the ETDRS visual acuity protocol
• No previous treatment with pan-retinal laser photocoagulation
• No substantial non-diabetic ocular condition that, in the opinion of the ophthalmologist, would impact diabetic retinopathy or diabetic macular oedema progression during the trial
• No substantial media opacities that would preclude successful imaging
• Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
• Subjects presently classified as being in New York Heart Association (NYHA) Class IV
• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR less than 30 ml/min/1.73 m^2
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly effective contraceptive methods
• Current or previous (within 30 days before screening) treatment with any glucagon like peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase-4 (DPP-4) inhibitor
• Receipt of any investigational medicinal product within 30 days before screening
• Previous participation in this trial. Participation is defined as randomisation
• Known or suspected hypersensitivity to trial products or related products
• Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

1. Is 8 to 17 years of age, inclusive, at the time of randomization/initiation of study drug administration. 2. Has received a diagnosis of T1D according to the criteria from the American Diabetes Association. 3. Is able to be randomized and initiate study drug within 6 weeks (42 days) of the formal T1D diagnosis. 4. Has a peak stimulated C-peptide of ≥0.2 pmol/mL from a mixed meal tolerance test (MMTT) at screening. 5. Has a positive result on testing for T1D-related autoantibodies. 1. Has any autoimmune disease other than T1D with the exception of stable thyroid or celiac disease. 2. Has an active infection and/or fever. 3. Has a history of or serologic evidence at screening of current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). 4. An individual who has a medical, psychological or social condition that, in the opinion of the Principal Investigator, would interfere with safe and proper completion of the trial.

• Has a confirmed diagnosis of endogenous Cushing syndrome
• Meets at least one of the following criteria:
• Has Type 2 diabetes mellitus
• Has impaired glucose tolerance
• Has hypertension
• Has non-endogenous source of hypercortisolemia
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
• Has poorly controlled hypertension
• Has poorly controlled diabetes mellitus
• Has severe renal insufficiency

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
• Male or female.
• Age above or equal to 18 years at the time of signing informed consent.
• Diagnosed with T2D greater than or equal to 180 days prior to the day of screening.
• HbA1c above 7.0% (53 mmol/mol) as measured by central lab.
• Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
• Stable daily dose(s) greater than or equal to 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regimen(s): a .Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. b .Any metformin combination formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. c. Any of the following non-insulin antidiabetic drug classes including combinations (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose):i). Sulfonylureas ii). Meglitinides (glinides) iii). DPP-4 inhibitors iv. SGLT2 inhibitors v). Thiazolidinediones vi). Alpha-glucosidase inhibitors vii). Oral combination products (for the allowed individual Oral Antidiabetic Drugs (OADs)) viii). Oral or injectable GLP-1-receptor agonists
• Intensification with insulin is indicated to achieve glycaemic target (4.4-7.2 mmol/L, 80-130 mg/dL) at the discretion of the treating investigator.
• Known or suspected hypersensitivity to trial product(s) or related products.
• Previous participation in this trial. Participation is defined as signed informed consent.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
• Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening. (Simultaneous participation in a trial with the primary objective of evaluating an approved or non-approved investigational medicinal product for prevention or treatment of COVID-19 disease or postinfectious conditions is allowed if the last dose of the investigational medicinal product has been received more than 30 days before screening)
• Any disorder which in the investigator's opinion might jeopardise subject's safety

• Shows lack of cortisol suppression
• Suppressed or low early-morning ACTH levels
• A radiologically confirmed adrenal lesion
• Has IGT or DM
• Has uncontrolled hypertension
• Has severe, uncontrolled hypertension
• Has poorly controlled DM
• Has significantly abnormal liver test results or severe renal insufficiency
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism

1. Willing to provide Informed Consent 2. Participants must live in a location with rapid access to emergency medical services 3. Age 18-45 years (both inclusive) at the time of signing informed consent 4. Must have a diagnosis of T1D for less than 48 months at randomization 5. Must have at least one diabetes-related autoantibody present (GAD65A; mIAA, if obtained within 10 days of the onset of insulin therapy; IA-2A; ICA; or ZnT8A) 6. Must have stimulated C-peptide levels greater than or equal to 0.2 pmol/ml measured during an MMTT conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization 7. Be willing to comply with intensive diabetes management 8. HbA1c ≤8.5% at screening 9. Subjects who are CMV and/or EBV seronegative at screening must be CMV and/or EBV PCR negative within 37 days of randomization and may not have had signs or symptoms of a CMV and/or EBV compatible illness lasting longer than 7 days within 37 days of randomization 10. Be up to date on recommended immunizations 11. Be at least 6 weeks from last live immunization 12. Be at least 4 weeks from killed vaccine other than flu vaccine 13. Participants are required to receive killed influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available 14. Be willing and medically acceptable to postpone live vaccines during the treatment period and for 3 months following last dose of study drug 15. If participant is female with reproductive potential, she must have a negative pregnancy test at screening and be willing to avoid pregnancy using a highly effective contraceptive method for the 12 months of the study 16. Males of reproductive age must use adequate contraceptive method during the treatment phase and for 3 months following last dose of study drug 17. Participants are required to receive an authorized non-live COVID-19 vaccination and be fully vaccinated, including eligible boosters as indicated, at least two weeks prior to randomization. Potential participants must not meet any of the following exclusion criteria: 1. One or more screening laboratory values as stated 1. Leukocytes < 3,000/μL 2. Neutrophils <1,500 /μL 3. Lymphocytes <800 /μL 4. Platelets <100,000 /μL 5. Haemoglobin <6.2 mmol/L (10.0 g/dL) 6. Potassium >5.5 mmol/L or <3.0 mmol/L 7. Sodium >150mmol/L or < 130mmol/L 8. AST or ALT ≥2.5 times the upper limits of normal 9. Bilirubin ≥ 1.5 times upper limit of normal 10. Glomerular Filtration Rate (eGFR) value of eGFR < 60 ml/min/1.73 m2 as defined by KDIGO 2012 (43) 11. Any other laboratory abnormality that might, in the judgment of the investigator, place the subject at unacceptable risk for participation in this trial 2. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening 3. Use of other immunosuppressive agents including chronic use of systemic steroids. Topical products are acceptable (nasal, conjunctival, skin) 4. Have active signs or symptoms of acute infection at the time of randomization 5. Have current, confirmed COVID-19 infection 6. Chronic active infection other than localized skin infections 7. Have evidence of prior or current tuberculosis infection as assessed by PPD, interferon gamma release assay or by history 8. Have evidence of current or past HIV, Hepatitis B infection 9. Have evidence of active Hepatitis C infection 10. Vaccination with a live virus within the last 6 weeks and killed vaccine within 4 weeks (except 2 weeks for flu vaccine) 11. Be currently pregnant or lactating, or anticipate getting pregnant within the one-year study period. 12. Have severe obesity: adults BMI ≥ 40 13. Have a history of malignancies 14. Untreated hypothyroidism or active Graves' disease 15. History of severe reaction to prior vaccination 16. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days after last blood draw (or 5 half-lives of investigational drug, whichever is greater) before screening, or currently enrolled in any other clinical trial 17. Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the trial 18. Supine blood pressure at screening outside the range of 90-139 mmHg for systolic or 50-89 mmHg for diastolic. To exclude white-coat nervousness a single repeat measurement is allowed 19. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk 20. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

1. ≥ 18 years of age 2. Histopathological or cytologically documented locally advanced or metastatic solid tumors who have no available standard therapeutic treatment options 3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 5. Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin (Hgb) ≥ 8 g/dl
• Platelets (plt) ≥ 75 x 10^9/L
• AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present
• Total bilirubin ≤ 1.5 x ULN
• Calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault formula) 6. Negative pregnancy test within 72 hours before starting study treatment in all premenopausal women and women < 12 months after the onset of menopause 7. Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 6 months after ceasing study treatment 8. Able to sign informed consent and comply with the protocol 1. Women who are pregnant or lactating 2. Women of child-bearing potential (WOCBP) who do not use adequate birth control 3. Patients with any hematologic malignancy, including leukemia (any form), lymphoma, and multiple myeloma 4. Patients with a history of primary central nervous system tumors or carcinomatous meningitis. 5. Patients with the following mood disorders as judged by the Investigator or a psychiatrist:
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
• ≥ CTCAE grade 3 anxiety 6. Impaired cardiac function or significant diseases, including but not limited to any of the following:
• left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
• Congenital long QT syndrome
• QTcF ≥ 480 msec on screening ECG
• Unstable angina pectoris ≤ 3 months prior to starting study drug
• Acute myocardial infarction ≤ 3 months prior to starting study drug 7. Patients with:
• unresolved diarrhea ≥ CTCAE grade 2, or
• impairment of gastrointestinal (GI) function, or
• GI disease that may significantly alter the absorption of TT-00420 8. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., uncontrolled hypertension, uncontrolled hypertriglyceridemia, or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol 9. Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy 10. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy 11. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy 12. Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 4 weeks prior to starting study drug. 13. Patients who are currently receiving treatment with therapeutic doses of warfarin sodium or any other coumarin-derivative anticoagulants 14. Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study drug or who have not recovered from the side effects of such treatment. 15. Patients who are currently receiving treatment with strong CYP3A inhibitors or inducers ≤ 2 weeks prior to starting study drug. 16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory; patients with well controlled HIV might be enrolled) 17. Known history of active infection with Hepatitis B or Hepatitis C 18. Has received a live-virus vaccination within 30 days of planned first dose 19. Inability to swallow or tolerate oral medication 20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial.

Inclusion Criteria
• CKD Inclusion Criteria (present at least ≥ 3 months apart) 1. There will be two or more Estimated Glomerular Filtration Rate (eGFRs) calculations less than 60ml/minute (corrected for BSA) or 2. Two or more positive tests for albuminuria and/or proteinuria Albuminuria/proteinuria can be defined by quantitative criteria with albumin/creatinine ratio greater than 30mg/g, urine protein creatinine ratio greater than 200mg/g or positive dipstick with protein detection (adjusted for urinary concentration/specific gravity).
• Diabetes Inclusion Criteria Only patients with type 2 diabetes will be enrolled in this study. 1. Random blood glucose greater than 200mg/dL 2. Hemoglobin A1C greater than 6.5% 3. Use of hypoglycemic agents or 4. Type 2 diabetes included in problem list
• Hypertension Inclusion Criteria 1. Systolic blood pressure greater than 140 mmHg on two different occasions at least one week apart 2. Diastolic blood pressure greater than 90 on two occasions at least more than one week apart 3. Use of antihypertensive agents except thiazide diuretics or 4. Hypertension included in problem list
• Exclusion criteria will be minimal in this pragmatic trial. The collaborative model of care will not be implemented in patients younger than 18 years or older than 85 years of age or patients who have CKD stage 5/End Stage Renal Disease(ESRD.
• Primary care practitioners have the option of not implementing the intervention on any of their patients if they believe benefit to be minimal or risk too high due to patient comorbidities

• Age 13-17 receiving ongoing medical care in the Diabetes Clinic at Children's Medical Center Dallas.
• Patients must be fluent in English (the materials on the site have not been validated in any other language), be in at least the 8th grade, report/demonstrate comfort with use of a computer, and regular, convenient and discreet access to the internet.
• Patients must experience at least sub-threshold depression (CES-D score > 15).
• Patients must have had the diagnosis of type 1 diabetes for at least 12 months.
• Patients who are medically unstable during their diabetes clinic visit will be excluded (i.e. diabetes ketoacidosis, symptomatic hypoglycemia).
• Patients who are too severely depressed for this form of intervention (i.e. meet criteria for MDD, endorse suicidal intent, PHQ-A score ≥ 20), those with a diagnosis or symptoms of severe mental illness (schizophrenia, bipolar disorder), prior psychiatric hospitalization, prior self-harm attempt.
• Patients receiving ongoing counseling or therapy services within the last year, by a licensed professional (counselor, psychologist or psychiatrist).
• Patients who are currently taking or begin taking psychotropic medications during study participation will be excluded/withdrawn.

• Participant is currently diagnosed with and/or being treated for secondary hyperparathyroidism (SHPT).
• Participant must be diagnosed with chronic kidney disease (CKD) stage 5 receiving peritoneal dialysis (PD) or hemodialysis (HD) for at least 30 days prior to initial Screening.
• For entry into the Washout Period (for vitamin D receptor activator [VDRA] non-naive participants), the participant must meet the appropriate laboratory criteria based upon the participant's age as described in the protocol.
• For entry into the Dosing Period (for VDRA-naive participants or VDRA non-naive participants who have completed the Washout Period), the participant must meet the appropriate laboratory criteria based upon the participant's age as described in the protocol.
• Participant is expected or scheduled to receive a kidney transplant within 6 months of Screening or is a kidney transplant recipient.
• Participant is expected to discontinue peritoneal dialysis (PD) or hemodialysis (HD) within 6 months of the initial Screening visit.
• Participant has had a parathyroidectomy within 12 weeks prior to Screening.
• Participant is taking maintenance calcitonin, bisphosphonates, glucocorticoids (in a dose equivalent to more than > 0.16 mg/kg/day or 5 mg prednisone/day, whichever is lower), 4 weeks prior to Dosing.
• Participant is receiving calcimimetics at the time of Screening or is expected to initiate calcimimetics at any time throughout the study.
• Participant is unable to take oral medications.

1. Adequate cognitive ability to consent and recall symptoms over a 1-week time period 2. Males and females ≥18 years of age with documented diagnosis of ornithine transcarbamylase deficiency (OTCD) confirmed with genetic testing, or willing to consent to OTC gene sequencing and deletion/duplication testing 3. Subject's ornithine transcarbamylase deficiency (OTCD) is stable as evidenced by 1. no clinical symptoms of hyperammonemia AND b, 2. an ammonia level <100 µmol/L (170 µg/dL) at the screening evaluation Subjects must remain free from symptoms of hyperammonemia throughout the screening period. 4. If using nitrogen ammonia scavenger therapy, must be on a stable regimen (no change in dose or frequency) for ≥ 28 days prior to providing informed consent and throughout the screening period 5. Must have maintained a stable protein-restricted diet (+/- amino acid supplementation) for at least 28 days prior to providing informed consent and continue to maintain a stable diet for the duration of the study 6. Good general health other than OTCD, in the opinion of the Investigator 7. Willing to refrain from strenuous exercise/activity and alcohol for 72 hours before study visits 8. Willingness to comply with procedures and visits 9. Willingness to follow contraception guidelines 1. History of clinically significant disease(s), in the opinion of the Investigator 2. Clinically significant screening laboratory values 3. Uncontrolled diabetes 4. Clinically significant anemia 5. Subjects who develop infection during screening must be asymptomatic for at least 7 days prior to dosing 6. Unwillingness to comply with study requirements 7. History of positive HIV, hepatitis C, or chronic hepatitis B 8. Uncontrolled hypertension 9. Malignancy within 5 years prior to study 10. Treatment with another investigational drug, biological agent, or device within 30 days of screening, or 5 half-lives of investigational drug 11. Treatment with any oligonucleotide or mRNA within 6 months of screening, with exceptions for some vaccinations and investigational treatments 12. History of gene therapy, hepatocyte or mesenchymal stem cell transplantation 13. Prior organ transplant 14. History of severe allergic reaction to a liposomal product 15. Recent history of, or current, drug or alcohol abuse 16. Dependence on inhaled (smoked or vaped) or oral cannabis products 17. Systemic corticosteroids within 6 weeks prior to screening 18. Blood donation of 50 to 499 mL within 30 days of screening or of .499 mL within 60 days of screening 19. Other conditions, in the opinion of the Investigator, that would make the subject unsuitable for participation

• Major
• Have completed a Corcept-sponsored study of relacorilant in endogenous Cushing syndrome with at least 80% compliance with the dosing schedule.
• According to the Investigator's opinion will benefit from continuing treatment with relacorilant
• Major
• Premature discontinuation from a relacorilant parent study.
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
• Has poorly controlled hypertension
• Has Stage ≥ 4 renal failure

• Male or female aged above or equal to 18 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus (T2D) 180 days or more prior to the day of screening.
• HbA1c from 7.0-11.0% (53.0-96.7 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
• Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
• Stable daily dose(s) 90 days or more prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s): a. Any metformin formulations at least or greater than 1500 mg or maximum tolerated or effective dose. b. Any metformin combination formulations equal to or above 1500 mg or maximum tolerated or effective dose. c. Any of the following oral anti-diabetic drug classes including combinations ((equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose): Sulfonylureas, Meglitinides (glinides), dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose co-transporter-2 (SGLT2) inhibitors, Thiazolidinediones, Alpha-glucosidase inhibitors, Oral combination products (for the allowed individual oral anti-diabetic drugs), Oral or injectable glucagon-like peptide 1 (GLP-1) receptor agonists
• Body mass index (BMI) equal to or below 40.0 kg/m^2.
• Any episodes (as declared by the subject or in the medical records) of diabetic ketoacidosis within 90 days prior to the day of screening.
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
• Chronic heart failure classified as being in New York Heart Association Class IV at screening.
• Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination

• Diagnosis of diabetes mellitus
• Subject is willing and able to wear a sports-style tube sock at least 22 hours a day.
• Ankle Brachial Index (ABI) ≥0.5 (bedside ABI is acceptable for screening purposes as the formal imaging ABI may not be resulted prior to surgery) or toe pressure of ≥30mmHg
• One or more diabetic foot ulcers (only one will be treated) that are located in the ankle area or below that has persisted a minimum of 30 days prior to the Screening visit
• Diabetic Foot Ulcers ≥1cm2 and ≤16cm2
• Ulcer grade I or II, Stage A, I or II Stage B, according to University of Texas Wound Classification System
• 22 years of age or older
• Has clinically significant renal disease to require hemo or peritoneal dialysis
• Subject has untreated osteomyelitis
• Ulcers within 5cm of target ulcer or connected by fistulas
• Ulcer has decreased by 30% or more at the end of the run-in period
• Subject has untreated cellulitis
• Subject has untreated charcot
• Major immunodeficiency including HIV
• Is pregnant or plans to become pregnant
• Is nursing or actively lactating
• Developmental disability/significant psychological disorder that in the opinion of the investigator could impair the subject's ability to provide informed consent, participate in the study protocol or record study measures, including untreated schizophrenia, bipolar disorder and psychiatric hospitalization within the last 2 years.
• Active alcohol or substance abuse in the opinion of the investigator that could impair the subject's ability to provide informed consent, participate in the study protocol or record study materials

• Patients must have histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug Administration (FDA)-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI)
• Patients who have previously received other forms of immunotherapy (high-dose [HD] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
• Age >= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky >= 60)
• Life expectancy of greater than 12 weeks
• Leukocytes >= 2,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN unless the patient has dermatomyositis and in the opinion of the investigator the elevation is due to diabetes mellitus (DM)
• Creatinine ULN OR glomerular filtration rate (GFR) >= 30 mL/min (if using the Cockcroft-Gault formula)
• Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
• If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
• If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
• Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the screening period. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
• The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted, if all of the following criteria are met:
• Repeat imaging demonstrates no new sites of bone metastases
• The lesion being considered for palliative radiation is not a target lesion
• Patients with prior therapy with an anti-PD-1 or anti-PD-L1
• Patients with prior allogeneic hematologic transplant
• Patients who are receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) bleeding, obstruction, and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. For the IBD (UC and CD) cohort, an endoscopic assessment, disease activity index, and disease specific inclusion/exclusion criteria will substitute for these factors in determining eligibility with the exception of abdominal carcinomatosis, which should prompt further evaluation

1. Be willing and able to adhere to the study procedures, including all requirements at the study center and return for the follow-up visit. 2. Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency CAH. 3. Be on a stable regimen of steroidal treatment for CAH. 4. Patients of childbearing potential must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) or other highly effective contraception during the study. 1. Have a diagnosis of any of the other known forms of classic CAH. 2. Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy. 3. Have a clinically significant unstable medical condition or chronic disease other than CAH. 4. Have a history of cancer unless considered cured. 5. Are pregnant. 6. Have a known history of clinically significant arrhythmia or abnormalities on ECG. 7. Have a known hypersensitivity to any corticotropin releasing hormone antagonists. 8. Have received any other investigational drug within 30 days before initial screening or plan to use an investigational drug (other than the study drug) during the study. 9. Have current substance dependence, or current substance (drug) or alcohol abuse. 10. Have had a blood loss ≥550 mL or donated blood or blood products within 8 weeks prior to the study.

Inclusion Criteria 1. Age between 23 and 75 years, inclusive, at screening. 2. AGHD Diagnosis Criteria For adult-onset AGHD: documented history of structural hypothalamic-pituitary disease, hypothalamic-pituitary surgery, cranial irradiation, 1-4 non-GH pituitary hormone deficiencies, a proven genetic cause of GHD, or traumatic brain injury (TBI). A. For all countries except Japan: Subjects must satisfy at least one of the following criteria: 1. Insulin tolerance test: peak GH ≤5 ng/mL 2. Glucagon stimulation test according to body mass index (BMI)
• i. BMI ≤30 kg/m2: peak GH ≤3 ng/mL
• ii. BMI >30 kg/m2: peak GH ≤1 ng/mL 3. Three or four pituitary axis deficiencies (i.e., adrenal, thyroid, gonadal, and/or vasopressin; not including GH) with IGF-1 SDS ≤ -2.0 at screening 4. Macimorelin test: peak GH ≤2.8 ng/mL 5. Growth hormone releasing hormone (GHRH) + arginine test according to BMI:
• i. BMI <25 kg/m2, peak GH <11 ng/mL
• ii. BMI ≥25-≤30 kg/m2, peak GH <8 ng/mL
• iii. BMI >30 kg/m2, peak GH <4 ng/mL B. For Japan only: Subjects with adult onset AGHD and deficiency of one or more other pituitary hormones need to satisfy at least one of the following criteria, while subjects with isolated GHD and no evidence of intracranial structure disorder (structural hypothalamic-pituitary disease) or with adult onset AGHD without deficiency of other pituitary hormones need to satisfy at least 2 of the following criteria: 1. Insulin tolerance test: peak GH ≤1.8 ng/mL 2. Glucagon test: peak GH ≤1.8 ng/mL 3. Growth Hormone Releasing Peptide-2 (GHRP-2) tolerance test: peak GH ≤9 ng/mL 3. IGF-1 SDS ≤ -1.0 at screening as measured by central laboratory. 4. hGH treatment naïve or no exposure to hGH therapy or GH secretagogue for at least 12 months prior to screening. 5. For subjects on hormone replacement therapies for any hormone deficiencies other than GH (e.g., adrenal, thyroid, estrogen, testosterone) must be on adequate and stable doses for ≥6 weeks prior to and throughout screening. 6. For subjects not on glucocorticoid replacement therapy, documentation of adequate adrenal function at screening defined. 7. For males not on testosterone replacement therapy: morning (6:00
•10:00AM) total testosterone within normal limits for age. 8. On a stable diet and exercise regime at screening with no intention to modify diet or exercise pattern during the trial, i.e., no weight reduction program intended during the trial or within the last 90 days prior to or through screening. 9. No plans to undergo bariatric surgery during the trial. 10. Normal fundoscopy at screening (without signs/symptoms of intracranial hypertension or diabetic retinopathy above stage 2 / moderate). For subjects with a diagnosis of diabetes mellitus at screening, this must be documented with a fundus photograph. 11. Able and willing to provide a written informed consent and authorization for protected health information (PHI) disclosure in accordance with Good Clinical Practice (GCP). Exclusion Criteria 1. Known Prader-Willi Syndrome and/or other genetic diseases that may have an impact on an endpoint. 2. Diabetes mellitus at screening if any of the following criteria are met: 1. Poorly controlled diabetes, defined as HbA1c >7.5% at screening. 2. Diabetes mellitus (defined as HbA1c ≥6.5% and/or fasting plasma glucose ≥126 mg/dL and/or plasma glucose ≥200 mg/dL two hours after oral glucose tolerance test) diagnosed <26 weeks prior to screening 3. Change in diabetes regimen (includes dose adjustment) within <90 days prior and throughout screening 4. Use of any diabetes drugs other than metformin and/or DPP-4 inhibitors for a cumulative duration of greater than 4 weeks within 12 months prior to screening 5. Diabetes-related complications at screening (i.e., nephropathy as judged by the investigator, neuropathy requiring pharmacological treatment, retinopathy stage 2 / moderate and above within 90 days prior to screening or during screening) 3. Active malignant disease or history of malignancy. Exceptions to this exclusion criterion: 1. Resection of in situ carcinoma of the cervix uteri 2. Complete eradication of squamous cell or basal cell carcinoma of the skin 3. Subjects with GHD attributed to treatment of intracranial malignant tumors or leukemia, provided that a recurrence-free survival period of at least 5 years prior to screening is documented in the subject's file based on a Magnetic Resonance Imaging (MRI) result 4. Evidence of growth of pituitary adenoma or other benign intracranial tumor within the last 12 months before screening. 5. Subjects with acromegaly without remission / with documented remission less than 24 months prior to screening. 6. Subjects with Cushing's disease without remission / with documented remission less than 24 months prior to screening. 7. Subjects with prior cranial irradiation or hypothalamic-pituitary surgery: the procedure took place less than 12 months prior to screening. 8. eGFR <60 mL/min/1.73m2 determined based on Modification of Diet in Renal Disease (MDRD) equation. 9. Hepatic transaminases (i.e., AST or ALT) >3 times the upper limit of normal. 10. Heart failure NYHA class 3 or greater (NYHA 1994). 11. QTcF ≥ 451 milliseconds on 12-lead ECG at screening. 12. Poorly controlled hypertension. 13. Cerebrovascular accident within 5 years prior to screening. 14. Anabolic steroids (other than gonadal steroid replacement therapy) or oral/intravenous/intramuscular corticosteroids within 90 days prior to or throughout screening. 15. Currently using or have used within 26 weeks prior to screening any weight-loss or appetite-suppressive medications. 16. Known history of hypersensitivity and/or idiosyncrasy to any of the test compounds (somatropin) or excipients employed in this trial. 17. Known history of neutralizing anti-hGH antibodies. 18. Inability to undergo scanning by DXA or a non-interpretable DXA scan at screening. 19. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive methods 20. Male subjects must use a condom, or his female partner of childbearing potential must use an effective form of contraception as described above, from the beginning of screening to the last trial visit. 21. Known substance abuse or known (or previous) eating disorders, including anorexia nervosa, bulimia and severe gastrointestinal disease affecting normal eating (as judged by the investigator). 22. Any disease or condition that, in the judgement of the investigator, may make the subject unlikely to comply with the requirements of the trial or any condition that presents undue risk from the investigational product or procedures. 23. Participation in another interventional clinical trial involving an investigational compound within 26 weeks prior to screening or in parallel to this trial.

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