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

Eligibility last updated 1/23/23. Questions regarding updates should be directed to the study team contact

• Subject is willing and able to provide written informed consent.
• Subject is willing and able to provide up to 50 mL of blood via venipuncture and comply with all other study and sample collection procedures.
• Subject is a female aged 18 through 49 years (inclusive).
• Subject is scheduled to undergo either:
  • Laparotomy or laparoscopy for signs and symptoms of suspected endometriosis;
  • Laparotomy, laparoscopy, or other procedures including, but not limited to, tubal ligation, lysis of adhesions, hysterectomy for benign condition, myomectomy, salpingo-oophorectomy, cystectomy, or diagnostic laparoscopy for indications including, but not limited to, infertility or benign gynecological indications. 

Exclusion Criteria:

• Subject has a history of surgically determined diagnosis of endometriosis (either via visual inspection or histopathology).
• Subject is a female in a pre-menarchal or post-menopausal state or has been rendered surgically menopausal (bilateral oophorectomy) for at least 6 months at Screening.
• Subject is pregnant.
• Subject has an active malignancy.
• Subject is known to have tested positive for human immunodeficiency virus or hepatitis A, B, or C.
• Subject has an active pelvic infection or other infections contraindicated for surgery.
• Subject has participated (+/-3 months of study enrollment) in a clinical trial where an investigational drug was or is planned to be administered.
• Subject is undergoing or has previously undergone masculinizing hormone therapy (testosterone treatment).
• Subject has any general health or behavioral condition that, in the opinion of the investigator, should exclude the subject from participation.

Eligibility last updated 9/21/21. 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.

• Diagnosis of multiple myeloma (MM) and/or amyloidosis (Systemic AL or ATTR).
• Age ≥ 18 years old.
• Planned monitoring and/or treatments as per standard of care for the incident disease.
• Anticipated return to clinic within 1-4 weeks of study enrollment, for a clinic visit that includes pre-visit PAC.

• Age < 18 years old.
• Diapated return to clinic within 1-4 weeks of study enrollment, for a clinic visit that includes pre-visit PAC.

• Age ≥ 18 years.
• BMI ≤ 30.
• No current cardiac medications.
• Systolic BP ≤ 140 mmHg.
• Diastolic BP ≤ 90 mmHg.
• Capacity to consent.

• Age < 18 years.
• To be assessed via EMR screening.
• Patient confirmation during screening visit.
• Screening tests as applicable.
• History of cardiovascular disease.
• eGFR < 30.
• Current orthopedic limitations.

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

• Practicing Vascular Surgeon at Mayo Clinic Rochester.
• Male or female.

• Uunable/willing to participate in all ascepts of the study.
• Primarily work at a site other than Rochester.
• Have any unknown history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder adherence.

• Adult female subjects aged 18 to 75 years, inclusive, or adult male subjects aged 50 to 75 years, inclusive, at the time of signing the ICF prior to initiation of any study-specific activities/procedures.
• A current diagnosis of symptomatic PAH classified by one of the following:
  • Idiopathic PAH (IPAH) or heritable pulmonary arterial hypertension (HPAH);
  • PAH associated with connective tissue diseases (CTD-APAHs):
    • Systemic sclerosis;
    • Mixed CTD or overlap syndrome;
    • Systemic lupus erythematosus.
  • Other CTD established by ACR/EULAR guidelines;
  • PAH associated with anorexigen or methamphetamine use;
  • Congenital heart disease with simple systemic to pulmonary shunt at least 1 year after surgical repair.
• 6MWD ≥ 150 meters and ≤ 550 meters at screening.
• WHO FC II or III symptomatology.
• Treatment with standard of care PAH background therapies.
• Documentation of cardiac catheterization within the screening period that is consistent with the diagnosis of PAH and meeting all the following criteria, to be confirmed by a central hemodynamic core laboratory:
  • Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg (at rest);
  • Pulmonary capillary wedge pressure ≤ 15 mmHg, or mean left atrial pressure (mLAP) or left ventricular-end diastolic pressure (LVEDP) ≤ 15 mmHg in the absence of left atrial obstruction;
  • PVR ≥ 400 dyne•s/cm^5.
• Pulmonary function tests (PFTs) at screening with the following criteria met:
  • Forced expiratory volume in 1 second (FEV1) divided by the forced vital capacity (FVC) ≥ 760% (predicted);
  • Total lung capacity (TLC) or FVC ≥ 70% predicted.

• Evidence of chronic thromboembolic disease or acute pulmonary embolism as assessed by ventilation-perfusion (V/Q) scan, computed tomography (CT)-angiogram, or pulmonary angiogram prior to screening.
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mm Hg or sitting diastolic blood pressure > 100 mm Hg during screening visit after a period of rest.
• Systolic blood pressure < 90 mm Hg during screening and baseline visits.
• WHO Pulmonary Hypertension Group 2-5.
• Human immunodeficiency virus (HIV)-associated PAH.
• History of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
  • Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency, mild aortic stenosis (AS), mild mitral stenosis (MS), moderate mitral regurgitation (MR);
  • Mechanical cardiac valve requiring anticoagulation;
  • Pericardial constriction or pericardial effusion with tamponade physiology;
  • Restrictive cardiomyopathy;
  • Left ventricular ejection fraction (LVEF) ≤ 50% by echocardiography (ECHO) within 6 weeks prior to screening; if  ECHO from the prior 6 weeks is not available, the screening ECHO results may be used to establish this criterion.
  • Note: If ECHO images are not adequate to provide an accurate estimate of LVEF then a multigated acquisition (MUGA) or cardiac magnetic resonance imaging (cMRI) scan or single photon emission computed tomography (SPECT) imaging can be used to obtain an accurate LVEF.
  • Left Atrial Area greater than 29cm2 by ECHO within 6 weeks prior to screening; if historical ECHO from the prior 6 weeks is not available, screening ECHO results may be used to establish this criterion. g. Documented uncontrolled symptomatic coronary disease (ie, unstable angina or percutaneous coronary intervention or coronary artery bypass graft within 12 months prior to screening, or planned coronary intervention or coronary artery bypass surgery).
• Untreated obstructive sleep apnea.
• History of atrial septostomy within 180 days prior to screening.
• Pulmonary venous occlusive disease (PVOD).
• Subjects with a history of portopulmonary hypertension or portal hypertension due to cirrhosis classified as Child-Pugh Class A or higher; or baseline ALT or AST > 2 x ULN or Total Bilirubin ≥ 2 X ULN.
• History of malignancy within 5 years prior to screening, with the exception of localized nonmetastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix.
• History of a potentially life-threatening cardiac arrhythmia with an ongoing risk.
• Uncontrolled bacterial, viral, or fungal infections which require systemic therapy.
• Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or IP administration (eg, history of intracranial hemorrhage), or absolute neutrophil count (ANC) < 1 x 10^9 /L or platelet count < 50 x10^ 9 /L.
• Any musculoskeletal disease or any other disease that limits evaluation of 6MWT.
• Pregnant or nursing or intends to become pregnant during the duration of the study.
• Body weight < 40 kg at screening.
• Chronic renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m^2 via CKD-epi (Levey, 2009) at screening or requires dialytic therapy or hemofiltration.
• Hemoglobin (Hgb) concentration < 8.5 g/dL at screening.
• Evidence of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, or tuberculosis (TB) infections.
• Inhaled prostanoids; these drugs may be withdrawn ≥ 4 weeks prior to screening, if clinically indicated.
• Use of oral anticoagulants (i.e., coumadin warfarin or novel oral anticoagulants [NOAC]) at randomization; if on coumadin warfarin or a NOAC, these drugs can be withdrawn, if clinically appropriate, during the screening period, and subjects should have normal coagulation parameters prior to the randomization for examples of prohibited anticoagulants).
• Requirement of intravenous (IV) inotropes (i.e., levosimendan, dopamine, dobutamine, milrinone, norepinephrine) other than an IV prostanoid within 4 weeks of screening. Prior/Concurrent Clinical Study Experience.
• Prior participation in GB002 studies and/or prior treatment with GB002.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device for the treatment of PAH within 4 weeks prior to screening.
  • Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks or at least 5 half-lives (whichever is greater) after the last dose of the previous investigational agent.
• Current use of inhaled tobacco and/or inhaled marijuana.
• Current alcohol use disorder as defined by DSM-5 and/or a positive test for drugs of abuse (amphetamines, methamphetamines, cocaine, phencyclidine [PCP]). Retest may be performed for potential false positive results. Subjects with a history of methamphetamine abuse must be abstinent for a minimum of 1 year prior to screening, in the opinion of the investigator.as documented by at least two negative urine or serology tests during the 12 months prior to screening. Certain drugs may be allowed IF prescribed by medical personnel and is under medical supervision for documented medical conditions (ie, opioids for pain, benzodiazepines for anxiety). Ingestible or topical marijuana is allowed, per local restrictions and regulations.
• Subjects with a history of severe milk protein allergy. In addition, subjects with known intolerance or hypersensitivity to lactose who, in the opinion of the investigator, may experience severe symptoms following the ingestion of lactose. 
• QTcF of > 480 msec recorded on a screening or baseline ECG or receiving concurrent treatment with medications that prolong QT interval. 
• Have any other condition or reason that, in the opinion of the Investigator or Medical Monitor, would prohibit the subject from participating in the study.

Eligibility last updated 1/25/22. Questions regarding updates should be directed to the study team contact.

• Eligible patients are females with stage I-III breast cancer taking adjuvant AI (either standard dose of anastrozole 1 mg daily or letrozole 2.5 mg daily or exemestane 25 mg daily) for greater than 30 days experiencing AI induced musculoskeletal pain scores of 5 or higher on a Likert scale will be enrolled. Treating physicians determine if pain is secondary to an AI.  
• ≥ 18 years old.
• Subjects should have completed any planned surgery for breast cancer, chemotherapy and radiation therapy at least 30 days prior to enrollment.
• Patients should have an ECOG performance score of 0-2. 

•  Age less than 18 years.
• Significant underlying pulmonary disease.

Eligibility last updated 1/14/22.  Questions regarding updates should be directed to the study team contact.

Patient

• Adults ≥ 18 years with biopsy proven resected NSCLC.
• Appointment to discuss adjuvant treatment of resected NSCLC.

Patient

• Major barriers to providing informed consent (i.e. dementia, severe hearing or visual impairment).

Clinician

• Clinicians who meet with patients to discuss adjuvant treatment of resected NSCLC.

Clinician

• None.

PAG Member

• Adults ≥ 18 years.
• Member of the KER Unit PAG.

PAG Member

• None.

Eligibility last updated 1/28/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Cohorts 1 and 4:

• Patients having relapsed/refractory, biopsy-proven grade 1, 2 or 3A, FL or MZL.
• ECOG performance status 0 to 2.
• Have received at least one prior line of treatment.

Inclusion Criteria
•Cohort 2:

• Patients having newlydiagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL.
• ECOG performance status 0 or 1.
• Patients not be in need of standard of care therapy according to the assessment of the treating physician.
• Patients with only one prior treatment and a high-risk profile as defined by first progression of disease within 24 months of diagnosis (the exclusion is not applicable for patients with more than one prior line treatment).

Inclusion Criteria
•Cohort 3:

• Patients having newly-diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL.
• ECOG performance status 0 or 1.
• Low tumor burden by Groupe d'Etude des Lymphomes Folliculaires criteria.
• Patients in need of therapy according to the assessment of the treating physician.

Inclusion Criteria
•Cohorts 1-4:

• Patients with an age ≥ 18 years old.
• Patients who are human leukocyte antigen (HLA)-A2 positive.
• Patients should have radiologically measurable disease with a lymph node or tumor mass greater than or equal to 1.5 cm in at least one dimension.
• Males or non-pregnant, non-lactating, females.
• Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
• Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures.

• Patients treated with dexamethasone > 2 mg/day or equivalent (i.e., 13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14 days before the first EO2463 administration, unless required to treat an adverse event.
• Patients with grade 3B FL or transformation to an aggressive lymphoma subtype.
• Patients with only one prior treatment and a high-risk profile as defined by first progression of disease within 24 months of diagnosis (the exclusion is not applicable for patients with more than one prior line treatment).
• Patients with prior exposure to EO2463.
• Patients treated with immunotherapy (meaning immunostimulatory or immunosuppressive therapy; beside excluded, or allowed, compounds per other inclusion/exclusion criteria specifications), radionuclide therapy, radiotherapy, cytoreductive therapy, or received treatment with any other investigational agent within 28 days before the first EO2463 administration.

Exclusion Criteria
•Cohorts 1 and 4:

• Patients who have received rituximab or other B cell ablation therapy within 8 weeks of start of study treatment.

Exclusion Criteria
•Cohorts 1-4:

• Patients with abnormal laboratory values.
• Patients with persistent Grade 3 or 4 toxicities.
• Uncontrolled central nervous system (CNS) metastasis.
• Other malignancy or prior malignancy with a disease-free interval of less than 3 years.
• Patients with clinically significant disease.
• Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g., Guillain-Barré syndrome).
• Patients with history of solid organ transplantation or hematopoietic stem cell transplantation.
• Pregnant and breastfeeding patients.
• Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.

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

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

• Healthy adults between the ages of 18 and 45.

• Individuals < 18 or > 45 years of age.
• Pregnant women (testing will be done by research team if requested).
• History of pulmonary, neurologic, cardiovascular, or musculoskeletal diseases.

Eligibility last updated 10/26/21. Questions regarding updates should be directed to the study team contact.

• Pathologically (histologically or cytologically) proven diagnosis of recurrent or persistent ovarian endometrioid or clear cell carcinoma, OR recurrent or persistent endometrioid endometrial adenocarcinoma; patients with recurrent endometrial cancer must have mismatch repair (MMR) immunohistochemistry completed; if they are found to be mismatch repair deficient, they should be offered treatment with immune checkpoint inhibition before consideration for treatment on trial; primary ovarian tumors must be at least 50% endometrioid or clear cell morphology, or have histologically documented recurrence with at least 50% endometrioid or clear cell morphology; institutional pathology reports must be provided indicating at least 50% endometrioid or clear cell morphology for ovarian tumors (primary or recurrent lesions).
• All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be ≥ 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray; lymph nodes must be > 15 mm in short axis when measured by CT or MRI.
• Patients must have had at least one, but no more than 3, prior cytotoxic regimens for management of primary disease; unlimited prior hormonal therapy, targeted therapy (including immunotherapy) or antiangiogenic therapy will be permitted.
• Patients must have completed prior therapy:
  • Chemotherapy: cytotoxic
    • At least 28 days since last dose of chemotherapy prior to registration.
  • Chemotherapy: nitrosoureas
    • At least 6 weeks since last dose of chemotherapy prior to registration.
  • Chemotherapy: non-cytotoxic (e.g. small molecule inhibitor)
    • At least 28 days since last dose of chemotherapy prior to registration.
  • Monoclonal antibody(ies)
    • At least 28 days since last dose of monoclonal antibody prior to registration.
  • Immunotherapy
    • At least 28 days since last dose of immunotherapy prior to registration.
  • Radiotherapy (RT)
    • At least 14 days from last local site RT prior to registration,
    • At least 21 days from stereotactic radiosurgery prior to registration.
    • At least 12 weeks from craniospinal, ≥ 50% radiation of pelvis or total body irradiation prior to registration.
    • Patients with central nervous system (CNS) disease should demonstrate evidence of stabilization after the 28-day time point after definitive treatment.
    • Full recovery of radiation related side effects prior to registration.
    • All subjects must have evidence of measurable disease outside of the radiation field at the time of registration.
• Appropriate stage for study entry based on the following diagnostic workup:
  • History/physical examination within 14 days prior to registration;
  • Imaging of the chest, abdomen and pelvis within 28 days prior to registration.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to registration.
• Platelets ≥ 100,000/mcl (within 14 days prior to registration).
• Absolute neutrophil count (ANC) ≥ 1,500/mcl (within 14 days prior to registration).
• Hemoglobin (Hgb) ≥ 8 g/dL (within 14 days prior to registration).
• Differential with no clinically significant morphologic abnormalities on complete blood count (CBC) testing; manual differential is encouraged, if clinically indicated, and in cases where an automated differential is abnormal (within 14 days prior to registration).
• Creatinine ≤ 1.5 x institutional/laboratory upper limit of normal (ULN) (within 14 days prior to registration).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (within 14 days prior to registration).
• Total serum bilirubin level ≤ 1.5 x ULN; direct bilirubin ≤ ULN for subjects with total bilirubin > 1.5 x ULN (patients with isolated indirect bilirubin elevations and a history of Gilbert's syndrome are eligible) (within 14 days prior to registration).
• Women of childbearing potential must be willing and able to use adequate contraception (hormonal and barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; theoretically, CYP3A induction with tazemetostat use may result in the loss of efficacy in hormonal contraceptives, thus a barrier method of contraception must be used in addition to hormonal contraceptives due to the potential drug-drug interaction with tazemetostat.
• The patient or a legally authorized representative must provide study-specific informed consent and authorization permitting release of personal health information prior to study entry.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

• Prior treatment with an investigational EZH2 inhibitor.
• Patients who are unable to swallow pills or absorb orally administered medication.
• A prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
• Abnormalities known to be associated with MDS (e.g., del 5q, chr 7 abn) and myeloproliferative neoplasms (MPN) (e.g., JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing.
• A prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL).
• Severe, active co-morbidity per the treating investigator's discretion.
• Pregnant or lactating patients.
• Known human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with tazemetostat; in addition, treatments involved in this protocol may be immunosuppressive, increasing the risk of lethal infections in this patient population.
• Treatment with strong inhibitors or inducers of CYP3A within 14 days of registration and during the study treatment.

• Patients aged 6 or older that have completed participation on active drug and demonstrated adequate safety and meaningful clinical benefit (efficacy) in a previous setmelanotide study for obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway.
  • Note: The index study may have a primary endpoint relied on efficacy, safety or tolerability. Patient will be eligible for extension study if the Primary Investigator believes the patient exhibited a clinically meaningful benefit (i,e, efficacy) to setmelanotide treatment, and would benefit from continued treatment, after discussion with the Sponsor.
• Study participant and/or parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and to understand and sign the written informed consent/assent. The patient must assent/consent to participate in the trial.
• Female participants of child-bearing potential must agree to use contraception as outlined in the protocol.
• Female participants of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months (and confirmed with a screening FSH level in the postmenopausal lab range), or have delayed pubertal development and failure to have achieved menarche, do not require contraception during the study.
• Any female participant in this latter category of having failed to reach menarche upon study entry and who now suspects this status may have changed should promptly inform the investigator and undergo pregnancy testing. All patients must agree to follow requirements for contraception.

• Pregnant and/or breastfeeding women.
• Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of a screening comprehensive skin evaluation performed by a qualified dermatologist. Any concerning lesions identified during the screening period will be biopsied and results known to be benign prior to enrollment. If the pre-treatment biopsy results are of concern, the patient may need to be excluded from the study.
• Patient is, in the opinion of the Study Investigator, not suitable to participate in the study. In addition, any patient who experiences a gap in treatment of at least one month between completing the Index study and Screening for this study, should have the following exclusion criteria evaluated:
• Current, clinically significant disease, if severe enough to interfere with the study and/or would confound the results. Any such patients should be discussed with the Sponsor prior to inclusion.
• Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic and Statistical Manual of Mental Disorders (DSM-III) disorders that the investigator believes will interfere significantly with study compliance.
• A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15.
• Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS). Any lifetime history of a suicide attempt, or any suicidal behavior in the last month.
  • Note: Patients who are unable to complete the PHQ-9 or C-SSRS due to significant neurocognitive defects may be enrolled in the study, as long as in the opinion of the Primary Investigator there are no clinical signs or symptoms of suicidal behavior.
• History of significant liver disease or liver injury, or a current liver assessment due to abnormal liver tests (as indicated by abnormal liver function tests, alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum bilirubin > 1.5 × the upper limit of normal [ULN] for any of these tests) for an etiology other than non-alcoholic fatty liver disease (NAFLD). Thus, any underlying etiology besides NAFLD, including diagnosed non-alcoholic steatohepatitis (NASH), other causes of hepatitis, or history of hepatic cirrhosis is exclusionary, but the presence of NAFLD is not be exclusionary.
• Moderate to severe renal dysfunction as defined by a glomerular filtration rate (GFR) < 30 mL/min.
• History or close family history (parents or siblings) of skin cancer or melanoma (not including non-invasive/infiltrative basal or squamous cell lesion), or patient history of ocular-cutaneous albinism.

Key Eligibility Criteria (additional criteria may apply) Part 1 Key Inclusion Criteria

1. Pathologically confirmed solid tumors, e.g., Colorectal Cancer (CRC), Non-Small Cell
Lung Cancer (NSCLC), or Pancreatic Cancer (PANC), that is metastatic, unresectable locally
advanced, or in the Investigator's opinion the subject is high risk for incurable relapse
within two years.

Part 1: Key Exclusion Criteria

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.

2. Prior allogeneic stem cell transplant.

3. Prior solid organ transplant.

Part 2 : Key Inclusion Criteria

1. Pathologically confirmed solid tumors, e.g., Colorectal Cancer (CRC), Non-Small Cell
Lung Cancer (NSCLC), Pancreatic Cancer (PANC), Mesothelioma, or Ovarian Cancer (OVAC)
that is metastatic, unresectable locally advanced, or in the Investigator's opinion
the subject is high risk for incurable relapse within two years.

2. Participants are germline HLA-A*02 heterozygous confirmed by HLA typing.

3. Primary tumor tissue showing LOH of HLA-A*02 by NGS testing.

4. Eastern Cooperative Oncology Group (ECOG) 0 or 1 performance status.

Part 2: Key Exclusion Criteria

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.

2. Prior allogeneic stem cell transplant.

3. Prior solid organ transplant.

4. Participants who have received any cancer therapy on any investigational therapy for
any indication, including but not limited to chemotherapy, small molecules, monoclonal
antibodies, or radiotherapy (with bone marrow impact) within 2 weeks of planned
apheresis or 3 half-lives, whichever is shorter.

5. 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 Intravenous (IV)
antimicrobials (e.g., IV antibiotics) or hospitalization (relating to completion of
antibiotic course).

6. Has known active central nervous system metastases. Subjects with previously treated
brain metastases may participate upon medical monitor agreement.

7. In the Investigator's judgement, any other condition or reason the subject would not
complete the required study visits and procedures, and follow up visits, or comply
with the study requirements for participation.

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

Eligibility last updated 3/10/23. Questions regarding updates should be directed to the study team contact.

• Have documented CD20+ B-cell malignancy, with active disease not responsive to prior therapy, for whom no standard of care options exists, and for whom treatment with an anti-CD20 antibody may be appropriate:
  • B-NHL confirmed by NCI working group criteria, 2007 (Cheson 2007) (Appendix 2);
  • CLL confirmed by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) working group criteria, 2008 (Hallek 2008) (Appendix 3).
• Patients with small lymphocytic lymphoma (SLL) will be enrolled in the CLL arm and follow NHL assessments.
• As of protocol amendment 16, enrollment is closed for CLL, FL grade 1-3a and aggressive lymphoma cohorts. The only cohort that remains open for enrollment is the DLBCL after failure of CAR-T therapy cohort.

• NOTE: A patient with CD20-negative lymph node (NHL) biopsy performed as standard of care just prior to enrollment, remains eligible for the study provided the patient had previously documented CD20+ disease AND was previously treated with rituximab or other CD20-directed antibody therapy within approximately 6 months. Individual cases may be discussed with the medical monitor.
• Patients with B-NHL must have had prior treatment with an anti-CD20 antibody therapy. Patients with CLL are not required to have received prior treatment with an anti-CD20 antibody therapy, provided the patient has failed either a BTK inhibitor or PI3K inhibitor and the treating physician deems it appropriate for the patient to be entered into a phase 1 trial. Refractory is defined as no response (SD/PD) or relapse within ≤6 months of last treatment. 
  • For inclusion in the FL grade 1-3a expansion cohort, patients must have received at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent; patients require failure of combination of lenalidomide plus rituximab where approved or not appropriate to receive this treatment according to the investigator. As of protocol amendment 16, enrollment is closed for patients with FL grade 1-3a;
  • For inclusion in the disease-specific expansion cohort enrolling DLBCL patients after failure of CAR-T therapy, the patient must have recovered from the toxicities of the lymphodepletion therapy and CAR-T infusion. There is no requirement for the prior CAR-T therapy to be the most recent line of therapy before study enrollment. Prior to enrollment, there must be verbal communication and documentation between the investigator and the medical monitor regarding prior toxicities associated with CAR-T therapy and their resolution;
  • Patients with aggressive lymphoma assigned to the aggressive lymphoma expansion cohort must have received at least one prior line of therapy consisting of an anti-CD20 antibody. Patients with prior CAR-T therapy will not be included in this cohort. As of protocol amendment 16, enrollment is closed for patients with aggressive lymphoma;
  • Patients with lymphoma eligible for the aggressive lymphoma expansion cohort include the following subtypes based on the WHO classification (Beham Schmid, 2017):
    • DLBCL not otherwise specified (NOS);
    • Germinal center B-cell type;
    • Activated B-cell type
    • Note: DLBCL includes both de novo DLBCL and transformed DLBCL arising from indolent lymphoma/CLL.
    • Primary mediastinal (thymic) large B-cell lymphoma;
    • T-cell/histiocyte-rich large B-cell lymphoma;
    • Epstein-Barr virus (EBV)+ DLBCL, NOS
    • High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements;
    • High-grade B-cell lymphoma, NOS;
    • B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma;
    • Follicular lymphoma, grade 3b.
• New enrollment of patients with MCL will be paused as of protocol amendment 15 until further risk mitigation measures are put in place for this patient population.
• All patients (B-cell NHL and CLL) must have at least one bi-dimensionally measurable lesion ≥ 1.5 cm on the longest diameter) documented by CT or MRI scan, if CT scan is not feasible.
• Patients with CLL must have white blood cell (WBC) ≤ 200 x 10^9/L. As of protocol amendment 16, enrollment is closed for patients with CLL. 
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Life expectancy of at least 6 months.
• Adequate bone marrow function documented by:
  • Platelet counts ≥ 75 x 10^9/L;
  • Hb level ≥ 9 g/dL;
  • ANC ≥ 1 x 10^9/L.
  • NOTE: Patients with cell counts below thresholds listed above may be considered for enrollment if, in the opinion of the investigator, the reason is believed to be due to bone marrow infiltration by underlying disease. In such cases,  the investigator must discuss the eligibility with the sponsor and receive approval for enrollment in writing.
• Adequate organ function documented by:
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN;
  • Total bilirubin ≤ 1.5 X ULN;
  • NOTE: Patients with Gilbert’s syndrome do not need to meet this requirement provided their total bilirubin is unchanged from their baseline.
  • Calculated creatinine clearance by Cockcroft-Gault ≥ 50 mL/min.
  • NOTE: Patients may be considered for enrollment if, in the opinion of the investigator, the abnormal laboratory results are due to underlying disease. In such cases, the investigator must discuss the eligibility with the sponsor and receive approval for enrollment in writing.
  • NOTE: Patients with borderline creatinine clearance by Cockcroft-Gault may be considered for enrollment if a measured creatinine clearance (based on 24-hour urine or other reliable method) is ≥ 50 mL/min.
• Willingness to undergo mandatory tumor biopsy pre-treatment, if in the opinion of the investigator, the patient has an accessible lesion that can be biopsied without significant risk to the patient.
• Willing and able to comply with clinic visits and study-related procedures.
• Provide signed informed consent.

• Primary central nervous system (CNS) lymphoma or known or suspected CNS involvement by non-primary CNS NHL.
• History of or current relevant CNS pathology such as:
  • Epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis; or
  • Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI.
• Standard anti-neoplastic chemotherapy (non-biologic) within 5-times the half-life or within 28 days, whichever is shorter, prior to first administration of study drug.
• Standard radiotherapy within 14 days of first administration of study drug.
  • NOTE: Palliative radiotherapy to a symptomatic lymph node/lesion is allowed provided the irradiated lesion(s) or node(s) is not included as a target lesion for tumor assessments.
• Allogeneic stem cell transplantation.
• Treatment with rituximab, alemtuzumab, or other investigational or commercial biologic agent within 12 weeks prior to first administration of study drug.
  • NOTE: for patients with aggressive lymphoma for which immediate treatment is required, the wash-out period may be reduced to 28 days. This will require discussion with and approval by the sponsor in writing.
• Immunosuppressive therapy (other than biologic) within 28 days of first administration of study drug.
• Treatment with an investigational non-biologic agent within 28 days of first administration of study drug.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition of study drug.
• History of hypersensitivity to any compound in the tetracycline antibiotics group.
• Concurrent active malignancy for which the patient is receiving treatment.
• Known active bacterial, viral, fungal, mycobacterial or other infection or any major episode of infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks of first administration.
• Evidence of significant concurrent disease or medical condition that could interfere with the conduct of the study, or put the patient at significant risk including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmias or unstable angina) and/or significant pulmonary disease (eg, obstructive pulmonary disease and history of symptomatic bronchospasm).
  • NOTE: Patients with a medical history of cardiac disease should be evaluated by ECHO or multi-gated acquisition scan (MUGA) prior to first administration of REGN1979 to ensure adequate cardiac reserves and function.
• Ongoing systemic corticosteroid treatment, with the exception of corticosteroid use for other (non-tumor and non-immunosuppressive) indications up to a maximum of 10 mg/day of prednisone or equivalent.
• Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).  Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted upon consultation with the physician managing the infection.
• Known hypersensitivity to both allopurinol and rasburicase.
• Pregnant or breast-feeding women.
• Women of childbearing potential* who are unwilling to practice highly effective contraception prior to the initial study drug treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; intrauterine device; intrauterine hormone-releasing system; bilateral tubal ligation; vasectomized partner; and or sexual abstinence†, ‡.
  • * Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
  • † Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.
  • ‡ Periodic abstinence (calendar, symptothermal and post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.
• Men who are unwilling to practice highly effective contraception prior to, during, and 6 months after the last dose.
• Administration of live vaccination within 28 days of first administration of study drug.
• Member of the clinical site study team and/or his/her immediate family, unless prior approval is granted by the Sponsor.

• Phase I only - Histologic confirmation of pancreatic, colorectal, gastroesophageal or biliary adenocarcinoma, as follows: 
  • Patients with metastatic disease from pancreatic cancer who received no more than 2 lines of prior therapy in the metastatic setting;
  • Patients with metastatic disease from colorectal cancer who received no more than 3 lines of prior therapy in the metastatic setting;
  • Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting;
  • Patients with metastatic disease from biliary tract cancer who received no more than 1 line of prior therapy in the metastatic setting.
  • NOTE: No prior exposure to irinotecan in the metastatic setting will be allowed except in the phase I dose escalation portion and in colon cancer patients only; in pancreas cancer, exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan. 
• Phase Ib only - Histologic confirmation of pancreatic or gastroesophageal adenocarcinoma, as follows: 
  • Patients with metastatic disease from pancreatic cancer who received no more than 1 line of prior therapy in the metastatic setting; 
  • Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting.
  • NOTE: No prior exposure to any irinotecan in the metastatic setting will be allowed.
• Phase II only - Patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD) or BRCA1 or BRCA2 or PALB2 mutation, or HRD (non-BRCA, non-PALB) who have not received any systemic therapy in the metastatic setting.
  • NOTE: In pancreatic cancer: exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan.
• Metastatic colorectal, pancreatic, gastroesophageal or biliary tract adenocarcinoma not amenable to curative resection.
• Measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Obtained ≤ 21 days prior to registration: Absolute neutrophil count (ANC) ≥ 1500/mm^3.
• Obtained ≤ 21 days prior to registration: Platelet count ≥ 100,000/mm^3.
• Obtained ≤ 21 days prior to registration: Hemoglobin > 9.0 g/dL.
• Obtained ≤ 21 days prior to registration: Total bilirubin ≤ institutional upper limit of normal (ULN).
• Obtained ≤ 21 days prior to registration: Aspartate transaminase (AST) ≤ 3 x ULN,  5.0 ≤ x ULN for patients with metastatic disease to the liver.
• Obtained ≤ 21 days prior to registration: Aminotransferase (ALT) ≤ 3.0 x ULN, ≤ 5.0 x ULN for patients with metastatic disease to the liver.
• Obtained ≤ 21 days prior to registration: Creatinine ≤ 1.0 mg/dL or creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula.
• Negative serum or urine pregnancy test done ≤ 7 days prior to registration and repeated prior to dosing on day 1 of each cycle, for individuals of childbearing potential only.
  • NOTE: Individuals are considered to be of childbearing potential unless one of the following applies.
  • Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause; a high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state; or 
  • Considered to be permanently sterile; permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy.
• Provide informed written consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
  • NOTE: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up. 
• Willing to provide tissue and blood samples for mandatory correlative research purposes.
• Individuals of reproductive potential and their partners willing to practice total abstinence or use a highly effective method of contraception (failure rate < 1% per year) during treatment and for 6 months following the last dose of rucaparib; the following are allowable only:
  • Ongoing use of progesterone-only injectable or implantable contraceptives (eg, Depo Provera, Implanon, Nexplanon); 
  • Placement of an intrauterine device or intrauterine system; 
  • Bilateral tubal occlusion; 
  • Sterilization, with appropriate post-vasectomy documentation of absence of sperm in ejaculate;
  • True, complete (as opposed to periodic) abstinence.

• Pregnant individuals.
• Nursing individuals.
• Persons of childbearing potential who are unwilling to employ adequate contraception.
• 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 human immunodeficiency virus (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.
• Previous or concurrent cancer that is distinct in primary site or histology from cancer of primary site ≤ 3 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, melanoma in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
  • NOTE: All cancer treatments for those distinct in a primary site other than cancer of origin must be completed ≥ 3 years prior to randomization.
• Received any prior poly ADP-ribose polymerase inhibitor (PARPi) treatment.
• Corrected QT interval (QTc) prolongation > 480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standard.

Eligibility last updated 2/28/22. Questions regarding updates should be directed to the study team contact.

• Be approaching the end of life. The primary criterion for identifying the patient’s prognosis is a referral to the PC team for discussion of goals of care. When the reason for referral to the PC team is unclear from the patient’s medical record the research assistant will ask the primary clinican whether they would be surprised if the patient died within the next 12 months. If the clinician responds they would not be surprised by that outcome then the patient will be determined to be eligible for participation in the study (Lynn, 2005; White et al., 2017).
• Be receiving palliative care in an inpatient, outpatient, or home care setting.
• Be age 18 or older.
• Be able to speak English.

• Is cognitively unable to complete study measures (Mini Mental Status Exam [MMSE] < 24).
• Has a history of psychosis (noted in medical record review).
• Is participating in another psychosocial intervention study focused on concepts similar to this study.

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

Eligibility last updated 7/26/22. Questions regarding updates should be directed to the study team contact.

• Aged 18 years of age or older.
• Patients who have had a recent episode of COVID-19 and who present to the Post COVID-19 Clinic at Mayo Clinic Rochester.   
• Access to smartphone (iOS or Android operating systems).
• Ability to complete study questionnaires and provide voice samples using a smartphone application.

• Known history of voice disorder either primary or secondary to neuromuscular or other pathology.
• Cognitively impaired patients.
• Prisoners.
• Non-English speakers.
• Currently on another study assessing depression or quality of life.

Eligibility last updated 2/22/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

- Adult patients ≥ 18 years of age undergoing primary liver transplant

- Ascites-adjusted BMI ≥ 25 kg/m2

- Acceptable graft function (total bilirubin level < 5 mg/dL and doppler ultrasound with
patent hepatic artery, hepatic veins and portal veins)

Exclusion Criteria

- Hepatocellular carcinoma (HCC) that did not fulfill Milan criteria as per explant
histology

- Untreated post-transplant vascular complications or biliary strictures

- Multi-organ transplantation

- Urine protein excretion ≥2.0 g/day

- Uncontrolled diabetes mellitus (HbA1c > 10%)

- Associated medical conditions incompatible with safe participation in a nutritional
intervention study, including digestive diseases with fat intolerance, neurological,
psychiatric or endocrine disorders

- Active eating disorder (e.g. bulimia nervosa, anorexia nervosa)

- History of bariatric surgery

- Pregnancy or planning on pregnancy in the next year

• ​​Age ≥ 18 and ≤ 80 years of age.
• Diagnosis of diabetes mellitus (type 1 or type 2).
• Both eyes meet the study eye criteria listed below.
• Able and willing to provide informed consent.
• Able and willing to wear a continuous glucose monitoring (CGM) device (for United States participants only).
• Either: (1) both eyes have mild- to- moderately severe NPDR (defined by ETDRS DR severity level 35 to 47) or (2) one eye has mild- to- moderately severe NPDR and the other eye has microaneurysms only (DR severity level 20).
• Confirmation of DR severity level is required by both the investigator and central Reading Center grading of fundus photographs.
• Both eyes must have best-corrected E-ETDRS visual acuity letter score ≥79 (approximate Snellen equivalent 20/25 or better).
• Both eyes must have media clarity, pupillary dilation, and study participant cooperation sufficient to obtain adequate fundus photographs, fluorescein angiogram, and OCT.
• Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality (including segmentation line placement.

• A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status that may preclude successful completion of follow-up).
• Initiation of intensive insulin treatment (a pump or multiple daily injections) within 3 months prior to screening or plans to do so in the next 3 months.
• Participation in an investigational trial that involved treatment within 30 days of screening with any drug that has not received regulatory approval for the indication being studied.
• Known allergy or hypersensitivity to any component of fenofibrate.
• Known allergy to fluorescein dye.
• History of treatment with a prescription fibrate medication (e.g. bezafibrate, fenofibrate, gemfibrozil, fenofibric acid) within 12 months prior to screening or anticipated need for fibrate medication for another indication (e.g. lipid management).
• Any prior systemic treatment for DME or DR.
• Decreased renal dysfunction, defined as requiring dialysis or central laboratory eGFR value < 60.
• Active liver disease, defined as any liver function test > 3 x upper limit of normal based on central laboratory value.
• Pre-existing symptomatic gallbladder disease including gallstones; however, prior gallbladder removal is not an exclusion.
• Triglycerides > 400mg/dL on treatment or > 700mg/dL on no treatment based on central laboratory value.
• Current use of any of the following medications:
  • Coumarin anticoagulants (Coumadin/Warfarin).
  • Immunosuppressants that affect kidney function, such as cyclosporine and tacrolimus.
  • Colchicine (Colcrys).
• History of severe myalgia requiring discontinuation of lipid lowering treatment.
• Blood pressure > 160/100 (systolic above 160 or diastolic above 100).
• HbA1c > 11.0% based on central laboratory value or if lab sample cannot be analyzed, recent result within 3 months.
• Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to screening or anticipated use during the study.
• For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 4 years.
• Participant is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next four years.
• The following exclusions apply to both eyes:
  • Evidence of definite neovascularization according to the investigator or central Reading Center grading of fluorescein angiography.
  • Includes presence of neovascularization (NV) outside of the 7-modified ETDRS fields on ultra-widefield imaging, which is an exclusion.
• Current CI-DME based on clinical exam or OCT central subfield thickness (CST), defined as:
  • Zeiss Cirrus: CST ≥ 290 µm in women or ≥ 305 µm in men.
  • Heidelberg Spectralis: CST ≥ 305 µm in women or ≥320 µm in men.
• Major non-diabetic intraocular pathology that in the opinion of the investigator would substantially and adversely affect visual acuity or lead to ocular neovascularization during the study.
• Any prior treatment for DME or DR.
• History of major ocular surgery within prior 4 months or anticipated within the next 6 months following randomization.
• Anticipated need for intraocular anti-VEGF or PRP in the next 6 months following randomization.
• History of intraocular anti-VEGF or corticosteroid treatment within the prior year for any indication.
• Any history of vitrectomy.
• History of YAG capsulotomy performed within 2 months prior to screening.
• Aphakia.
• Evidence of uncontrolled glaucoma (intraocular pressure must be <30, with no more than one topical glaucoma medication, and no documented glaucomatous field loss for the eye to be eligible).

Eligibility last updated 1/21/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years old and residing in the US.
• Clinical diagnosis, based on investigator assessment, of type 2 diabetes for at least one year.
• Using a stable insulin dose for at least 3 months, to include A) basal insulin only, or B) MDI, to include CSII (including use of AID systems other than Tandem Control-IQ).
• Total daily insulin dose ≤ 200 units/day.
• Willing to use only aspart (novolog) or lispro (humalog) insulin with the study pump, with no use of concentrated insulin above U-100, long-acting basal insulin injections, or inhaled insulin.
• For females, not currently known to be pregnant If female of childbearing potential, must agree to use a form of contraception to prevent pregnancy while a participant in the study as documented in the study records. A negative serum or urine pregnancy test will be required for all females of child-bearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.
• HbA1c ≥ 7.5% and ≤ 12% at screening.
• Has current glucagon product to treat severe hypoglycemia (injectable or nasal) at home (will provide prescription if they do not have one).
• Be willing to exercise for 30 minutes or more at least once per week during the main phase of the study.
• Has the ability to read and understand written English.
• Investigator believes that the participant has capacity such that they can provide informed consent and can successfully and safely operate all study devices and is capable of adhering to the protocol and completing the study.

• Prior use of Tandem t:slim X2 insulin pump with Control-IQ technology.
• Two or more episodes of severe hypoglycemia (needing assistance) in the past 6 months.
• History of inpatient psychiatric treatment in the past 6 months.
• History of drug abuse (defined as any illicit drug use) or history of alcohol abuse prior to screening or unwillingness to agree to abstain from illicit drugs throughout the study.
• History of significant heart disease, lung disease, liver disease, chronic kidney disease, or other systemic disease determined by investigator to interfere with the study, or make required exercise unsafe.
• History of significant vision, hearing, or dexterity problems that will impair use of the closed loop system.
• Use of glucocorticoids, beta blockers, sulfonylureas, meglitinides or other medications specifically listed in section 8.3 of the protocol or determined by investigator to interfere with the study.
• Unstable dose of SGLT-2 inhibitor, GLP-1 receptor agonist, or other adjuvant medication or starting a new glucose lowering agent during the trial.
• Unstable dose of any medication used for weight loss or starting a new medication for weight loss during the trial.　
• Abnormal screening electrocardiogram consistent with increased risk during exercise, such as arrhythmia, ischemia, or prolonged QTc interval (> 450 ms).
• History of hemodialysis.
• History of adrenal insufficiency.
• Uncontrolled hypo- or hyperthyroidism.
• Significant diabetes related complications, based on investigator assessment.
• Immediate family member (spouse, biological or legal guardian, child, sibling, parent) who is an investigative site personnel directly affiliated with this study or who is an employee of Tandem Diabetes Care, Inc.

Eligibility last updated 10/26/21. Questions regarding updates should be directed to the study team contact.

• Age 18+.
• English speaking.
• Consented for Outcomes Registry Study (15-000136).
• Undergoing radiotherapy for cancer treatment with curative intent.
• Willing to and able to give consent and participate in study.
• Willing to complete all questionnaires and surveys.
• Able to access a device (computer, smartphone, or tablet) with web access every day to complete study surveys.
• Willing to connect to a device (i.e., a smartphone, Fitbit or tablet) that can regularly link to Hugo for data transfer.
• Willing to use the Hugo health data sharing platform.
• Willing to create a Mayo Clinic Patient Portal (if not already created).

• Unable to give consent and enroll prior to administration of baseline survey.
• Partial breast RT (3 fraction), due to overlap in cadence used for all disease sites.
• SBRT to the lung, due to overlap in cadence used for all disease sites.
• Co-enrollment on another PRO related study (soft rule):
  • Coordinator would need to get source data from Adam via Hugo;
  • Response data will only be accessible by select people.

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

Eligibility last updated 10/20/22. Questions regarding updates should be directed to the study team contact.

• Only patients who completed studies UT001 or TC-BC-12 with a status of CR at the final FU visit.

• None.

• Subject must have a disease of interest. Specifically, subject must have one of:
  • head and neck squamous cell carcinoma (HNSCC);
  • non-small-cell lung cancer (NSCLC);
  • small cell lung cancer (SCLC);
  • urothelial carcinoma (UCC);
  • gastric or gastroesophageal junction adenocarcinoma;
  • cervical cancer;
  • esophageal squamous cell carcinoma (ESCC);
  • triple-negative breast cancer (TNBC); 
  • hepatocellular carcinoma (HCC);
  • renal cell carcinoma (RCC);
  • colorectal cancer (CRC).
• Subject must have received, or be scheduled to receive, at least one dose of anti-PD-1/PD-L1 immunotherapy for treatment of their cancer.
• Subject must have had, or will have, a tumor biopsy prior to treatment with anti-PD-1/PD-L1 immunotherapy.
• Subject must have undergone, or will undergo, medical imaging (e.g., CT or MRI) of the tumor prior to treatment with anti-PD-1/PD-L1 immunotherapy.
• Willing to provide electronic informed consent per IRB-approved protocol.
• Able to speak, read, and comprehend English fluently.
• Subject is 18 years of age or older.
• Subjects must have sufficient tissue available to fulfill the specimen requirements of the study, as defined in the SPECIMENS TO BE COLLECTED section of this protocol.

• Inability or unwillingness to provide informed consent.
• Subject who does/did not have one of the cancers listed above (other histologies).
• Subject has already participated in this trial.

• 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.

• 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.