Eligibility last updated 7/13/22. Questions regarding updates should be directed to the study team contact.

• Adult patient, aged 18 or older.
• English-speaking.
• Patients who have reported evidence of hiccups in the past five years.
• Patients who upon contact describe having had hiccups.

• Individuals < 18 years of age.
• Have not experienced hiccups in the past five years.

Eligibility last updated 8/16/21. Questions regarding updates should be directed to the study team contact.

• Previously participated in a prior study and expressed willingness to be recontacted or who respond to intramural and extramural adverts.
• We propose three groups: 10 individuals who have NFG/NGT, 10 individuals with prediabetes (IGT) and 10 individuals with type 2 diabetes (T2DM).

• Medications that can affect glucose metabolism (to be determined by PI) or in the case of participants with T2DM taking pioglitazone.
• For female subjects: positive pregnancy test.
• Any active systemic illness.
• Upper gastrointestinal surgery.

Eligibility last updated 8/20/21. Questions regarding updates should be directed to the study team contact.

• Participant must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
• [US/France] Participants with stable Upper Limb Spasticity (ULS) for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study.
• [Canada] Participants with stable post-stroke ULS for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study.
• Participants who are either naïve to Botulinum toxin type A (BoNT-A) for ULS or who have been previously treated with BoNT-A for ULS.
• Participants with MAS score of at least 2 at elbow, wrist and finger flexors.
• Participants with DAS score of at least 2 on the Principal Target of Treatment (PTT) (one of four functional domains: dressing, hygiene, limb position and pain).
• Participants who require BoNT-A injection in all of the following muscles: flexor carpi radialis, flexor carpi ulnaris, flexor digitorum profundus, flexor digitorum superficialis and biceps brachii.
• Participants for whom injection of a total dose of 900 Units aboBoNT-A or 360 Units onaBoNT-A is considered by the investigator to be clinically appropriate.
• Participants who have been stable for at least 3 months prior to study entry in terms of oral antispasticity, anticoagulant and/or anticholinergic medication if treated, and for at least 1 month prior to study entry in terms of occupational and/or physiotherapy treatment, if treated, and are considered by the investigator likely to remain stable for the duration of the study.

• Major limitations in the passive range of motion in the paretic upper limb.
• Major neurological impairment (other than limb paresis) that could negatively affect functional performance.
• Participants clinically requiring injection into any upper limb muscles other than the five muscles of one arm or requiring injection into both arms or any lower limb within the timeframe of the study.
• Hypersensitivity to any BoNT product or excipients.
• Hypersensitivity to cow's milk protein (casein).
• Infection at the proposed injection site(s).
• Known peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome).
• Any medical condition (including dysphagia or breathing difficulties/compromised respiratory function) that in the opinion of the investigator, might jeopardize the participant's safety.
• Women who are pregnant or lactating.
• Participants treated with BoNT of any type for any indication (e.g., bladder injection, headache or cosmetic) within the previous 12 weeks or planned/likely to be treated during the course of the study.
• Prior history of non-responsiveness to BoNT treatment.
• Previous surgery, or administration of alcohol or phenol in the study limb 6 months or earlier from study enrolment or planned/likely to be treated during the course of the study.
• Participants treated with intrathecal baclofen, aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), within the previous 4 weeks or planned/likely to be treated during the course of the study.
• Participants who received a COVID-19 vaccine injection within 7 days before the first planned study intervention injection, or planned/likely to be injected within 7 days after the first planned study intervention injection.

Eligibility last updated 8/16/21. Questions regarding updates should be directed to the study team contact.

• Men who are currently receiving androgen deprivation therapy (ADT) for the treatment of prostate cancer. ADT is defined by a history of orchiectomy, or ongoing usage of gonadotropin-releasing hormone agonists or antagonists.
• Men receiving next generation androgen axis inhibitor therapies including abiraterone, enzalutamide, apalutamide, and darolutamide are eligible.
• Patients must be on a stable dose of all hormone-directed therapies for at least 28 days prior to registration and must not be planning to discontinue this therapy for at least 42 days following registration.
• Patients receiving radiation therapy during the study period are eligible.
• Eligible patient must have bothersome hot flashes for ≥ 14 days prior to registration, defined by an occurrence of ≥ 28 times per week and of sufficient severity to cause the patient to seek therapeutic intervention.
• Life expectancy of greater than 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status
  •0, 1, or 2.
• In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English.

• No current use or future planned use of any of the following agents during the study period: drugs that are not Food and Drug Administration (FDA) approved for use in humans, androgens, estrogens, progesterone analogs, gabapentin, selective serotonin reuptake inhibitor (SSRI)/serotonin and norepinephrine reuptake inhibitor (SNRI) anti-depressants, cholinergic agonists, cholinesterase inhibitors, or complementary/alternative medicine taken for the purpose of managing hot flashes. Prior use of these agents is permitted as long as they are discontinued before registration.
• No current or prior use of oxybutynin.
• Patients with a history of any of the following contraindications to oxybutynin are not eligible:
  • gastroparesis or gastrointestinal obstructive disorders;
  • significant gastric reflux symptoms not controlled by medication; ulcerative colitis;
  • narrow-angle glaucoma;
  • urinary retention requiring indwelling or intermittent self-catheterization within the prior 6 months;
  • hypersensitivity to oxybutynin or any other components of the product; current uncontrolled hyperthyroidism;
  • uncontrolled coronary artery disease or a history of myocardial infarction within the prior 12 months;
  • New York Heart Association (NYHA) class II-IV congestive heart failure;
  • symptomatic cardiac arrhythmias;
  • current uncontrolled hypertension;
  • myasthenia gravis; or
  • dementia.

Eligibility last updated 11/22/21. Questions regarding updates should be directed to the study team contact.

• Diagnosis of functional nasal obstruction or aesthetic nasal concern requiring nasal surgery with costal cartilage harvest.
• Male or female with age ≥ 18 years.
• Willing and able to understand and provide written informed consent.

• Age < 18 years of age.
• Known pregnancy.
• Women who are currently nursing a child.
• History of coagulopathy; such as hemophilia or Von Willebrand disease, or any congenital or acquired bleeding disorder.
• Use of anticoagulation medication during the study; i.e. aspirin, Coumadin, Plavix, or medications similar in class to these medications will exclude the patient from participation.
• Inability to provide informed consent (patients under guardianship).
• Known hypersensitivity to local anesthetics
• History of cardiac disease; such as current impaired cardiovascular function, past history of myocardial infarction, congenital heart disease, current cardiac symptoms; i.e. angina, shortness of breath, or chest pain as determined by history or review of the medical record.
• History of complex pulmonary disease; such as uncontrolled asthma, COPD, or interstitial lung disease as determined by history or review of the medical record. 
• Impaired renal function as documented in the medical record in the last 3 months with a serum creatinine greater than 1.2 mg/dL or glomerular filtration rate < 60 mL/min/BSA as determined by history or review of the medical record.
• History of or current hepatic disease as documented by liver function test abnormality in the last 3 months as determined by history or review of the medical record. 

Eligibility last updated 8/16/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Participant:

• Age range 30- < 91 years with minimum life expectancy of at least 1 year.
• Willingness to return to study site for follow up at 1 month and 1 year.
• Fluent in English or Spanish.
• Willingness to have fingerstick blood sample collected to determine HbA1c level at entry and at 1 year. If determined to be diabetic at baseline, participant will be advised to seek medical care.

Inclusion Criteria
•Study Eye:

• Clinically recommended for DMEK, and able to schedule DMEK between 5 to 90 days after enrollment.
• Presence of a condition related to endothelial dysfunction which will be treated by DMEK.  Eligible indications for DMEK include:
  • Presence of Fuchs endothelial corneal dystrophy (FECD) meeting at least one of the following:
  • Phakic FECD with or without cataract;
  • Triple procedure including DMEK for FECD, cataract extraction and posterior chamber intraocular lens implantation (IOL) is allowed;
  • Pseudophakic FECD with posterior capsule supported, sulcus supported, or scleral-fixated posterior chamber IOL b. Pseudophakic corneal edema with posterior capsule supported, sulcus supported, or scleral-fixated posterior chamber IOL without FECD;
  • Failed Descemet stripping automated endothelial keratoplasty (DSAEK) or DMEK without exclusionary criteria, as described below.

• Pregnant or planning to become pregnant prior to the DMEK study surgery, based on verbal report.
• Lack cognitive capacity such that consent could not be provided.
• Presence of a condition that has a high probability for failure (e.g., failed penetrating keratoplasty, uncontrolled uveitis).
• Stromal vascularization that will impede assessment of recipient stroma clarity.
• Other primary endothelial dysfunction conditions including posterior polymorphous corneal dystrophy and congenital hereditary corneal dystrophy.
• Indication for surgery that is not suitable for DMEK (e.g, keratoconus, stromal dystrophies and scars).
• Aphakic corneal edema with or without FECD.
• Anterior chamber IOL in study eye prior to DMEK or planned placement of anterior chamber IOL during DMEK.
• Planned IOL exchange of an anterior chamber IOL with a posterior chamber IOL in study eye at time of study DMEK.
• Pre-operative central sub-epithelial or stromal scarring that could impact post-operative recipient stromal clarity assessment.
• Presence of anterior synechiae.
• Peripheral anterior synechiae in the angle greater than a total of three clock hours.
• Uncontrolled glaucoma with or without prior filtering surgery, tube shunt placement, or MIGS. Uncontrolled glaucoma is defined as intraocular pressure > 25mm Hg.
• Controlled glaucoma with prior tube shunt placement for glaucoma (controlled glaucoma with MIGS is allowed).
• Fellow eye visual acuity < 20/200 due to an ocular condition other than a cornea disease that would be a candidate for DMEK.
• IOP < 8 mmHg.
• Topical Rho kinase inhibitor, including Rhopressa, used within 1 month prior to study entry and anticipated during the course of the study.

Eligibility last updated 5/18/22. Questions regarding updates should be directed to the study team contact.

• Clinical diagnosis of diabetes based upon an elevated hemoglobin A1C.

• Diagnosis of Diabetic Nephropathy.
• Active or unresolved Diabetic Ketoacidosis (DKA).
• Steroid Induced Hyperglycemia.

Eligibility last updated 8/18/21. Questions regarding updates should be directed to the study team contact.

• Subjects with chronic kidney disease (estimated glomerular filtration rate < 60).
• Recruitment will primarily focus on patients with end stage renal disease who are being considered for renal transplantation or initiation of hemodialysis.
• Minorities will be included.

• Individuals < 18 years of age.
• Subjects not diagnosed with chronic kidney disease.

Eligibility last updated 8/18/21. Questions regarding updates should be directed to the study team contact.

• Patients must understand and provide written informed consent prior to initiation of any study-specific procedures.
• ≥ 18 years of age.
• Patients must have a diagnosis of confirmed malignancy.
• Patient is a good medical candidate for a standard of care or research biopsy or surgical procedure to obtain tissue or has tissue available for analysis that has been collected within 12 months of signing consent.

• Uncontrolled concurrent illness including psychiatric illness, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent.
• Inaccessible tumor for biopsy or patient does not have tumor tissue available for research use.
• Biopsy must not be considered to be more than minimal risk to the patient.
• Contraindications to percutaneous biopsy:
  • Significant coagulopathy that cannot be adequately corrected;
  • Severely compromised cardiopulmonary function or hemodynamic instability;
  • Lack of a safe pathway to the lesion;
  • Inability of the patient to cooperate with, or to be positioned for, the procedure.

Eligibility last updated 11/10/21. Questions regarding updates should be directed to the study team contact.

• Capable and willing to provide informed consent.
• Confirmed or suspected physician diagnosis of Primary Immunodeficiency.

• Not willing to provide consent.
• Not diagnosed with Primary Immunodeficiency.

Eligibility last updated 9/10/21. Questions regarding updates should be directed to the study team contact.

Stage 1 Key

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/15/22. Questions regarding updates should be directed to the study team contact.

​​​​​

• Male or female subjects aged 18 or older at the time of signed informed consent.
• In the opinion of the Investigator, there is no other meaningful life-prolonging therapy option available.
• Population:
  • Part 1: Must have documented diagnosis of ovarian cancer, endometrial cancer, colorectal cancer, gastric cancer, gastroesophageal junction cancer, triple negative breast cancer, non-small cell lung cancer, or cholangiocarcinoma.
  • Part 2 Stage 1: Must have one of the following cancer types indicated below with the corresponding expression level of FRα.:
  • Ovarian Cancer
    • Moderate and/or High
  • Endometrial Cancer
    • Moderate and/or High
  • Colorectal Cancer
    • Moderate and/or High
  • Gastric Cancer
    • Moderate and/or High
  • Gastroesophageal Junction Cancer
    • Moderate and/or High
  • Triple Negative Breast Cancer
    • Moderate and/or High
  • Non-small cell lung cancer
    • Moderate and/or High
  • Cholangiocarcinoma
    • Moderate and/or High
  • Specific cancer types from the table above will be selected by the Sponsor, in consultation with the Part 1 CSRC and other experts, at the conclusion of Part 1 Dose Escalation. In addition, moderate and high FRα expression thresholds will be defined and communicated by the Sponsor to Investigators upon completion of translational testing prior to the start of Part 2.

Part 2 Stage 2 or Registration Study:

• Must have documented FRα expression in one of the topoisomerase 1 inhibitor-sensitive tumor types evaluated in Part 2 Stage 1. Specific tumor groups will be selected by the Sponsor, in consultation with the CSRC and/or Steering Committee (SC) and other experts, at the conclusion of Part 2 Stage 1.
• Folate receptor α (FRα) expression:
  • Part 1: Must provide archival tumor tissue or a newly obtained tumor biopsy specimen prior to the first dose of study drug for retrospective FRα expression analysis. The availability of the FRα expression result is not required to start study drug administration.
  • Part 2: Must provide archival tissue or a newly obtained tumor biopsy specimen prior to the first dose of study drug for prospective determination of FRα overexpression at the Sponsor-designated laboratory. The FRα expression result is required prior to the initiation of study drug administration.
• In Part 1, measurable disease or, in the absence of measurable disease, non-measurable disease (lesions considered truly non-measurable include leptomeningeal disease, ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly identified by physical exam that is not measurable by reproducible imaging techniques), as per RECIST v1.1. In Part 2, measurable disease (only), as per RECIST v1.1.
  • Note:  A lytic or mixed lytic-blastic bone lesion with a soft tissue component assessed on CT/MRI can be measurable if the minimum size criteria are met.
• For other criteria, refer to RECIST v1.1.
• Expected survival of at least 3 months.
• In Part 1, Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or 2.
• In Part 2, ECOG Performance Status of 0 or 1.
• Adequate organ function defined as:
  • Absolute neutrophil count ≥ 1,500/μL;
  • Platelets ≥ 100,000/μL;
  • Hemoglobin ≥ 8 g/dL;
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (including subjects with documented Gilberts syndrome, liver metastases, or other etiologies);
  • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 5 x ULN;
  • Calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation.
• Recovered from any previous surgery and no history of major surgery within the last 28 days prior to start of study drug.
• For women of childbearing potential, willingness to avoid pregnancy by using an effective method of contraception from the first dose of ELU001 up to 5 times the half-life of ELU001 treatment (about 10 days) plus 6 months after the last dose of study drug (or longer, if required by Regulatory Authority or local practice).
• For males who are capable of fathering a child, willingness to take precautions that are effective in preventing pregnancy from the first dose of ELU001 and up to 5 times the half-life of ELU001 treatment (about 10 days) plus 3 months after the last dose of study drug (or longer, if required by Regulatory Authority or local practice).
• Willing and able to understand and comply with all aspects of the protocol.
• Provided informed consent prior to any protocol-related procedures, including screening evaluations.

• Clinically significant active or chronic corneal disorder.
• Received investigational anti-cancer treatment, other anti-neoplastic therapy, including cytotoxics, targeted agents, biological therapy including antibodies and endocrine therapies ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, prior to starting study drug, whichever is shorter.
• Require use of folate-containing supplements during the treatment period.
• Known medical history of:
  • Clinically significant cardiovascular and respiratory conditions including myocardial infarction within 1 year, uncontrolled or unstable angina, congestive heart failure (New York Heart Association [NYHA] Class III or IV), or arrhythmia (Grade 2 or higher), within 5 years;
  • Another malignancy within 3 years before the first dose, or previously diagnosed with another malignancy, and have any evidence of residual disease. Subjects with non-melanoma skin cancer or cervix carcinoma in situ, treated and radiated early prostate cancer if they have undergone complete resection, or chronic lymphocytic leukemia (CLL) who is on close monitoring and treatment is not required, are not excluded;
  • Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment;
  • Serious, uncontrolled medical disorder such as seizures, nonmalignant systemic disease, or active, uncontrolled infection or active infection causing fever. Examples include, but are not limited to, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. Subjects with chronic diseases that are well controlled (e.g., diabetes mellitus, hypertension (< 150 systolic blood pressure [sBP] and < 90 diastolic blood pressure [BP]) are eligible;
  • Part 1 only: Recognized immunodeficiency condition including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary, or congenital immunodeficiency’s (human immunodeficiency virus (HIV) infection, see below).
• Any of the following conditions (testing is not required in this protocol, unless required by Regulatory Authority or local practice)
  • Known HIV-infected subjects, unless on effective anti-retroviral therapy with an undetectable viral load within 6 months; or
  • Known or suspected hepatitis B if active infection (subjects with chronic hepatitis B infection must have an undetectable Hepatitis B Virus (HBV) viral load on suppressive therapy, if indicated; positive surface antibody alone is not an exclusion); or
  • Known or suspected hepatitis C infection which has not been treated and cured unless currently on treatment with an undetectable viral load.
• Active medical conditions of:
  • Subjects in Part 1 with autoimmune disease (e.g., rheumatoid arthritis, Systemic Lupus Erythematosus (SLE), ulcerative colitis, Crohn's Disease, Multiple Sclerosis (MS), ankylosing spondylitis, thyroiditis) requiring continuing immune suppressive therapy;
  • Subjects in Part 1 with brain or leptomeningeal metastases; in Part 2, subjects with symptomatic brain or leptomeningeal metastases with any lesion greater than 3 cm, or evidence of herniation or hemorrhage.
• Any of the following recent treatments or therapies:
  • Subject has received a transfusion (platelets or red blood cells) ≤ 2 weeks prior to first dose of study drug;
  • Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent in Part 1, except for inhalers or those on a pre-planned steroid taper.
  • Note: Premedication with corticosteroids to prevent or decrease the severity of infusion related reactions per institutional standard of care is allowed;
  • Chronically treated with systemic doses of other immunosuppressive drugs such as cyclosporine, methotrexate, adrenocorticotropic hormone (ACTH) or immune suppressive monoclonal antibodies.
• Female subjects who are lactating or breast feeding or have a positive pregnancy test within 7 days prior to first dose of study drug.
• Any condition(s) that, in the opinion of the Investigator, would increase the risk for toxicities from study drug, interfere with subject compliance or conduct of this study.
• In the opinion of the Investigator, there is significant risk to a subject when the tumor tissue biopsy specimen procedure is performed
• Subjects who have a QTcF > 470 ms within 4 weeks prior to the first dose of study drug.

Eligibility last updated 10/26/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 8/24/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

• Willing and able to provide written informed consent. If the subject is unable to consent for himself/herself, a legally authorized representative must provide informed consent on his/her behalf.
• Males or females ≥ 18 years of age.
• Evidence of candidemia or invasive candidiasis based on growth of Candida species from any of the following: blood, peritoneal fluid, intra-abdominal collection/abscess, pancreatic fluid/tissue, peripancreatic fluid, pleural fluid/tissue.

• Severe neutropenia (absolute neutrophil count < 500 cells/microL).
• Profound lymphopenia (< 300 cells/microL).
• The Principal Investigator (PI) is of the opinion that the subject should not participate in the study.

Eligibility last updated 8/23/21. Questions regarding updates should be directed to the study team contact.

• Diagnosis of imperforate anus.

• Lack of a parent or guardian to provide informed consent.

Eligibility last updated 9/24/21. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 12/16/22. Questions regarding updates should be directed to the study team contact.

• Adult female patients 18 to 99 years of age.
• Patients with proven breast cancer and nodal metastases referred for staging breast MR within the Department of Radiology.
• Patients who are able and willing to sign the informed consent.
• Negative pregnancy test if subject is of child-bearing age (females of child-bearing potential will be screened for pregnancy using a urine pregnancy test, which will be administered by the unit study coordinator at no cost to the patient).

• Minors under 18 years of age.
• Patients unable to provide written informed consent.
• Pregnancy.
• eGFR ≤ 30 (4,5).
• History of prior moderate or severe contrast reaction including unresponsiveness, severe respiratory distress, convulsions, arrhythmia, cardiopulmonary distress, progressive angioedema, laryngeal edema, dyspnea, bronchospasm, symptomatic tachycardia, symptomatic bradycardia, hypotension, hypertensive crisis.
• Any history of premedication prior to iodinated contrast.
• Patients that consent to participation but do not undergo their clinically indicated MR scanning for any reason (e.g., bad IV, infiltration, reaction, change in indication).

Eligibility last updated 8/24/21. Questions regarding updates should be directed to the study team contact.

• 18 years of age and older.
• Patient is a good medical candidate for a standard of care or research biopsy or surgical procedure to obtain tissue.

• Individuals < 18 years of age.
• Uncontrolled concurrent illness including psychiatric illness, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent.
• Inaccessible tumor for biopsy or patient does not have tumor tissue available for research use.
• Biopsy must not be considered to be more than minimal risk to the patient.
• Have a contraindication to percutaneous biopsy including:
  • Significant coagulopathy that cannot be adequately corrected;
  • Severely compromised cardiopulmonary function or hemodynamic instability;
  • Lack of a safe pathway to the lesion per the interventional radiologist;
  • Inability of the patient to cooperate with, or to be positioned for, the procedure.

Eligibility last updated 8/23/21. Questions regarding updates should be directed to the study team contact.

• Individuals ≥ 18 years of age.
• Adult kidney transplant recipients awaiting transplant, kidney transplant recipients and living kidney donors.

• Subjects under 18 years of age.

Eligibility last updated 9/28/21. Questions regarding updates should be directed to the study team contact.

• Patient presenting to a General Internal Medicine Service.
• Patient in one of the 3 Mayo Clinic Campuses (Rochester, Arizona, Florida).
• Patient with an undiagnosed mass: New or enlarging lymph nodes clinically or on imaging:
  • New mass on imaging of soft tissues, bone, spleen, adrenal gland, retroperitoneum, or intraabdominal location without clear organ association .
• Patient has understood and signed the informed consent to participate in the registry.
• Patient has the ability to complete all aspects of registry enrollment.
• Aged 18 and older.

• Mass involving the breast, brain, kidney, lung, ovary/adnexa, liver, pancreas, sinus, throat, or thyroid gland will be addressed by the respective specialty areas.  
• Patients with a known history of any condition or factor judged by the investigator to preclude participation in the registry or which might hinder adherence.
• Lacking the capacity to consent.
• Prisoners or institutionalized individuals.
• Pregnant women.

Eligibility last updated 9/17/21. Questions regarding updates should be directed to the study team contact.

Eligibility last updated6/7/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Study Arm 1 Preschool Children < 6 years old Asthma Group (N=200) :

• Diagnosis of asthma.
• In the absence of an asthma diagnosis:
  • Persistent wheezing of at least one year;
  • Even distribution of socio-demographics including age, gender, race and ethnicity.

• Actively sick with covid or flu.

Inclusion Criteria
•Non-Asthma/Disease Controls (N=200) :

• Diagnosis of allergy.
• Even distribution of sociodemographics including age, gender, race and ethnicity.

• Diagnosis of asthma.
• Recurrent wheezing.
• Actively sick with covid or flu.

Inclusion Criteria
•Healthy Controls (N=200) : 

• Not having or suspected of having any known upper/lower respiratory disease.
• Even distribution of sociodemographics including age, gender, race and ethnicity.

• Diagnosis of asthma or any known upper/lower respiratory disease.
• Diagnosis of allergy.
• Actively sick with covid or flu.

Inclusion Criteria
•Study Arm 2 Children 6-17 years of age Asthma Group (N=200) :

• Diagnosis of asthma.
• In the absence of an asthma diagnosis:
  • Persistent wheezing of at least one year.
• Even distribution of sociodemographics including age, gender, race and ethnicity.

• Actively sick with covid or flu.  

Inclusion Criteria
•Non-Asthma/Disease Controls  (N=200) :

• Diagnosis of allergy. 
• Even distribution of sociodemographics including age, gender, race and ethnicity.

• Diagnosis of asthma.
• Recurrent wheezing.
• Actively sick with covid or flu.

Inclusion Criteria
•Healthy Controls  (N=200) :

•  Not having or suspected of having any known upper/lower respiratory disease.
• Even distribution of sociodemographics including age, gender, race and ethnicity. 

• Diagnosis of asthma or recurrent wheezing.
• Diagnosis of allergy.
• Actively sick with covid or flu.

Inclusion Criteria
•Study Arm 3  Adults > 18 years old
Asthma Group (N=200) :

• Diagnosis of asthma.
• Even distribution of sociodemographics including age, gender, race and ethnicity. 

• Actively sick with covid or flu.  

Inclusion Criteria
•Non-Asthma/Disease Controls (N=200) :

• Diagnosis of allergy.
• Even distribution of sociodemographics including age, gender, race and ethnicity. 

• Diagnosis of asthma.
• Recurrent wheezing.
• Actively sick with covid or flu.

Inclusion Criteria
•Healthy Controls  (N=200) :

•  Not having or suspected of having any known upper/lower respiratory disease.
• Even distribution of socio-demographics including age, gender, race and ethnicity.

Exclusion Criteriao: 

• Diagnosis of asthma.
• Diagnosis of allergy.
• Actively sick with covid or flu.

Eligibility last updated 11/2/22. Questions regarding updates should be directed to the study team contact.

• Patient has provided informed consent
• Patient is willing and able to comply with clinic visits and procedures outlined in the study protocol
• Male or female, at least 18 years of age
• Patients must have an ECOG performance status of 0 or 1.
• Laboratory measurements, blood counts:
  • Hemoglobin must be ≥ 9 g/dL prior to initial dose of study treatment. Red blood cell
    (RBC) transfusions are allowed to meet hemoglobin eligibility within limits set per
    Exclusion Criterion #4 
  • Absolute neutrophil count (ANC) at least 1.5 x 10^9/L without growth factor support
    within 2 weeks of study treatment initiation
  • Platelets at least 100 x 10^9/L
• Laboratory measurements, renal function:
  • Patients must have adequate renal function as demonstrated by a creatinine clearance of at least 30 mL/min; calculated by the Cockcroft Gault formula
• Adequate liver function, as demonstrated by:
  • AST less than or equal to 2.5 x ULN or less than or equal to 5 x ULN in patients with liver metastases
  • ALT less than or equal to 2.5 x ULN or less than or equal to 5 x ULN in patients with liver metastases
  • Bilirubin less than or equal to 1.5 x ULN, or less than or equal to 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert’s syndrome or genetic equivalent
• Pretreatment blood cross-match completed (Section 7.8.1.1)
• Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 5.
• Measurable disease according to response evaluation criteria in solid tumors (RECIST),Version 1.1. Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.
• Patients must have a life expectancy of 3 months or greater, in the opinion of the investigator.

Safety Run-in Cohort 1 and Phase 2 Cohort 1
In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Safety
Run-in Cohort 1 and Phase 2 Cohort 1 must fulfill the following cohort-specific inclusion
criteria:

• Patients previously untreated for unresectable locally advanced or mTNBC that is histologically or cytologically confirmed based on the most recent analyzed biopsy or other pathology specimen, defined as negative for estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) according to the most recent American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline (Appendix 9).
• Patients whose tumors are considered PD-L1 negative, as determined by an approved test according to local standards.
• Prior systemic treatment for neoadjuvant and/or adjuvant therapy and/or curative intent radiation therapy is permitted if completed at least 6 months prior to enrollment.

Note: Maintenance therapies are not counted as separate lines of therapy.

Safety Run-in Cohort 2 and Phase 2 Cohort 2
In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Safety
Run-in Cohort 2 and Phase 2 Cohort 2 must fulfill the following cohort-specific inclusion
criterion:

• Patients with unresectable, locally advanced or mTNBC that is histologically or cytologically confirmed based on the most recent analyzed biopsy or other pathology specimen, defined as negative for ER, PR, and HER2 according to the most recent ASCO/CAP guideline (Appendix 9), who have received 1 prior line of therapy in the unresectable, locally advanced/metastatic setting. Patients must have been previously treated with a taxane in the neoadjuvant, adjuvant, or locally advanced/metastatic setting
• Patients with tumors considered positive for PD-L1 expression (as determined by an approved test according to local standards) must have received an immune checkpoint inhibitor for 1L treatment of locally advanced/metastatic disease

• Positive serum pregnancy test.
• Breastfeeding female.
• Active central nervous system (CNS) disease. Patients with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids for at least 4 weeks) are allowed.
• Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening. RBC transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criteria.
• History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.
• Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
• Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha-targeting agents.
• Current participation in another interventional clinical trial.
• Known inherited or acquired bleeding disorders.
• Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV
• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which patients are not on active anticancer therapies and who are in complete remission for over 2 years.
• Known active or chronic hepatitis B or C infection or human immunodeficiency virus infection in medical history).
• Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted.
• Uncontrolled pleural effusion.
• Uncontrolled hypercalcemia (ionized calcium >1.5 mmol/L) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.
• Uncontrolled tumor-related pain.
• Severe/serious systemic infection within 4 weeks of randomization.
• Rapid deterioration during screening prior to enrollment (eg, significant change in performance status, 20% or greater decrease in serum albumin levels or uncontrolled tumorrelated pain)
• Other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and followup
  examinations
• Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted
• Patients who have received a live vaccine within 30 days of randomization
   

Safety Run-in Cohort 1 and Phase 2 Cohort 1
Patients who meet the following exclusion criterion are not eligible to be enrolled into Safety
Run-in Cohort 1 or Phase 2 Cohort 1:

• Disease progression within 6 months following neoadjuvant/adjuvant therapy or rapid visceral progression and/or symptomatic disease, where single-agent chemotherapy would not be appropriate.

NOTE: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormonereleasing
hormone agonists for breast cancer, and treatment with bisphosphonates and receptor
activator of nuclear factor kappa B ligand inhibitors are not criteria for exclusion. There is no
required minimum washout period for these therapies. Patients should be recovered from the
effects of radiation.

Safety Run-in Cohort 2 and Phase 2 Cohort 2
Patients who meet any of the following exclusion criteria are not eligible to be enrolled into
Safety Run-in Cohort 2 or Phase 2 Cohort 2:

• Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and patients with a history of bowel obstruction or gastrointestinal perforation within 6 months of enrollment
• Patients who previously received topoisomerase I inhibitors or antibody-drug conjugates containing a topoisomerase inhibitor
• High-dose systemic corticosteroids (≥ 20 mg of prednisone or its equivalent) are not allowed within 2 weeks of Cycle 1 Day 1
• Have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs due to a previously administered agent
  • Note: patients with any grade neuropathy or alopecia are an exception to this criterion and will qualify for the study
  • Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

NOTE: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormonereleasing hormone agonists for breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa B ligand inhibitors are not criteria for exclusion. There is no required minimum washout period for these therapies. Patients should be recovered from the effects of radiation.

Eligibility last updated 2/18/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Progressive or recurrent WHO Grade IV IDH wildtype glioblastoma (including molecular glioblastoma and gliosarcoma).
• Have an enhancing mass on MRI amenable to resection or biopsy of the tumor (as determined by the neurosurgeon pre-operatively) and histological diagnosis of glioblastoma from a prior biopsy or surgery.
• Willing to undergo resection or biopsy of their glioblastoma at Mayo Clinic in Rochester, MN.
• ECOG Performance Status (PS) of 0 or 1 and KPS ≥ 70.
  • Note: PS must be assessed again within 7 days prior to first dose of study drug.
• The following laboratory values obtained ≤ 15 days prior to registration:
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
  • Platelet count ≥ 100,000/mm^3;
  • Hemoglobin ≥ 9.0 g/dL without transfusion or EPO dependency (≤ 7 days prior to assessment);
  • Creatinine ≤ 2.0 x ULN OR measured or calculated creatinine clearance (per institutional standard) must be ≥ 45 ml/min;
  • Total bilirubin ≤ 1.5 x ULN OR Direct bilirubin ≤ULN for patients with total bilirubin levels > 1.5 x ULN;
  • Aspartate transaminase (AST) AND alanine transaminase (ALT) ≤ 2.5 x ULN;
  • INR/PT/aPTT ≤ 1.5 × ULN OR if patient is receiving anticoagulant therapy then INR or aPTT is within target range of therapy.
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only (POCBP).
  • Note: If testing done for eligibility is > 72 hours prior to first dose, then pregnancy testing must be repeated, and result must be negative for patient to receive treatment.
• POCBP or able to father a child must be willing to use adequate contraception starting with first dose through 120 days after last dose. 
• Provide written informed consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willing to provide tissue and blood samples for correlative research purposes.

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:

• Pregnant persons.
• Nursing persons.
• Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception.
• Signs or symptoms of life-threatening raised intracranial pressure: as defined by the treating neurosurgeon, including severe headache, nausea, decreasing level of consciousness, precluding 4-7 day delay in scheduling neurosurgery.
• Prior treatment.
• Received bevacizumab (AVASTIN) ≤ 28 days prior to registration.
  Note: Bevacizumab is allowed for symptom control during the adjuvant phase if the study.
• Received a live vaccine ≤ 30 days prior to registration.
• Major surgery ≤ 28 days prior to registration.
• Requirement for dexamethasone dose of > 2mg/day ≤ 2 days prior to registration.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.
• 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.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy requiring systemic treatment ≤ 1 year prior to registration.
• History of myocardial infarction ≤6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Active autoimmune disease that has required systemic treatment (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) ≤ 2 years prior to registration.
  • Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Known history of active TB (Bacillus Tuberculosis).
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Hypersensitivity to pembrolizumab or any of its excipients.
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

• Group 1: HFpEF-CKD-will consist of 30 subjects with:
  • Ejection fraction of greater than 55%; and
  • Evidence of increased LV filling pressures, including at least 2 of the following:
  • average septal–lateral E/e’ ratio > 15;
  • tricuspid regurgitation (TR) peak velocity > 2:8 m/s;
  • Left atrial volume index >34mL/m^2 assessed by echocardiography; and
  • Previous diagnosis of HF with New York Heart Association (NYHA) functional class II-III symptoms on chronic loop diuretic therapy; and
  • CKD defined as glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m^2 as estimated by the Modification of Diet in Renal Disease equation. Subject needs to be on stable dose of chronic loop diuretic for at least 4 weeks prior to study and maintained on the same dose for the duration of the study. In addition to the exclusion criteria listed below, to ensure a more homogenous group of subjects, we will exclude subjects with Diabetes or BMI > 35 (because endogenous natriuretic peptide levels are low in obese subjects).
• Group 2: HFpEF-EI-will consist of 30 subjects with:
  • Ejection fraction of greater than 55%; and
  • Previous invasive determination of normal pulmonary capillary wedge pressure (< 15 mmHg) at rest and ≥ 25 mmHg during exercise12; and
  • New York Heart Association (NYHA) functional class II-III symptoms but not on chronic loop diuretic therapy; and
  • Glomerular filtration rate (eGFR) of > 60 mL/min/1.73 m^2 as estimated by the Modification of Diet in Renal Disease equation. In addition to the exclusion criteria listed below, to ensure a more homogenous group of subjects, we will exclude subjects with Diabetes or BMI>35 (because endogenous natriuretic peptide levels are low in obese subjects).

• Age < 18 years.
• Body mass index > 35.
• Blood pressure < 100/60 or > 180/100 mmHg.
• Diabetes.
• Myocardial infarction within 6 months of screening.
• Unstable angina within 6 months of screening, or any evidence of myocardial ischemia.
• Significant valvular heart diseases.
• Hypertrophic, restrictive or obstructive cardiomyopathy.
• Constrictive pericarditis.
• Primary pulmonary hypertension.
• Biopsy proven active myocarditis.
• Severe congenital heart diseases.
• Cardiac amyloidosis.
• Fabry disease.
• Sarcoidosis.
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening.
• Second or third degree heart block without a permanent cardiac pacemaker.
• Stroke within 3 months of screening, or other evidence of significantly compromised CNS perfusion.
• Hemoglobin < 9 g/dl.
• ALT > 2 times the upper limit of normal; serum sodium of  < 135 mEq/dL or > 150 mEq/dL.
• Serum potassium of < 3.5 mEq/dL or > 5.7 mEq/dL.
• Bother acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data.
• Received an investigational drug within 1 month prior to dosing.
• Patients with an allergy to iodine; female subject who is pregnant or breastfeeding.
• In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons.

Eligibility last updated 3/16/22. Questions regarding updates should be directed to the study team contact.

Key

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/19/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Part 1:

• Able to provide written informed consent.
• Pathologically confirmed solid tumors; e.g., Colorectal Cancer (CRC), Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer, Gastric and Esophageal Cancer, Ovarian Cancer, Mesothelioma, Breast Cancer, or Head and Neck Cancer and in the Investigator’s opinion the subject is high risk for incurable relapse within two years.
• Age ≥ 18 years.

Exclusion Criteria
•Part 1:

• History of any of other malignancy in the past 5 years other than non-melanoma skin carcinoma, low grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the Cervix, or Stage I uterine cancer.
• Prior allogeneic stem cell transplant.
• Prior solid organ transplant.
• In the investigator’s judgement, the subject is unlikely to complete all protocol required study visits, including hospitalization, study visits and procedures, and follow up visits, or comply with the study requirements for participation. 

Eligibility Criteria
•Part 2:

• Able to provide written informed consent.
• Pathologically confirmed solid tumors; e.g., Colorectal Cancer (CRC), Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer, Gastric and Esophageal Cancer, Ovarian Cancer, Mesothelioma, Breast Cancer, or Head and Neck Cancer and in the Investigator’s opinion the subject is high risk for incurable relapse within two years.
• Age ≥ 18 years.
• Subjects are germline HLA-A*02 heterozygous confirmed by HLA typing.
• Primary tumor tissue showing LOH of HLA-A*02 by NGS.
• Adequate bone marrow reserve, hematological, renal and hepatic function defined as: 
  • Hemoglobin > 9.0 g/dL;
  • ANC 800/µl;
  • Platelet count > 80,000/µl;
  • Serum Creatinine <1.5 x ULN;
  • Calculated Creatinine Clearance > 60 ml/min;
  • Total Serum Bilirubin < 2 x ULN;
  • ALT< 5 x ULN;
  • AST< 5 x ULN.
• Eastern Cooperative Oncology Group (ECOG) performance status < 1.
• Baseline oxygen saturation > 92% on room air.
• No clinically significant pleural effusion.

Exclusion Criteria
•Par 2:

• History of any of other malignancy in the past 5 years other than non-melanoma skin carcinoma, low grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the Cervix, or Stage I uterine cancer.
• Prior allogeneic stem cell transplant.
• Prior solid organ transplant.
• Presence of any indwelling catheter or drain (e.g., percutaneous nephrostomy tube, indwelling foley catheter, biliary drain, or pleural/peritoneal, pericardial catheter).  Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted.
• Subjects who have received any cancer therapy (investigational agent or not), including but not limited to chemotherapy, small molecules, monoclonal antibodies, or radiotherapy (with bone marrow impact) within 3 weeks of planned leukapheresis or 5 half-lives, whichever is shorter.
• Has a diagnosis of immunodeficiency or autoimmune disease requiring continued systemic therapy (e.g., monoclonal antibody therapy).
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment necessitating specific treatment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to completion of antibiotic course).
• Has known active central nervous system metastases. Subjects with previously treated brain metastases may participate upon sponsor agreement.
• Known or suspected chronic, active Epstein Barr Virus (EBV).
• Has known active history of or screened positive for Human Immunodeficiency Virus (HIV).
• Has known active history of or screened positive for Hepatitis B (HBsAg positive) or C (anti-HCV positive).
• Unstable angina, myocardial infarction, cardiac angioplasty or stenting, or any other significant cardiac disease within the last 6 months.
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
• Requires supplemental home oxygen.
• Significant pulmonary disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or obstructive pulmonary disease).
• Females of childbearing potential who are pregnant or breastfeeding.
• In the investigator’s judgement, the subject is unlikely to complete all protocol required study visits, including hospitalization, study visits and procedures, and follow up visits, or comply with the study requirements for participation. 

Eligibility last updated 11/10/21. Questions regarding updates should be directed to the study team contact.