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

Eligibility last updated 12/21/22]. Questions regarding updates should be directed to the study team contact.

• Male patients.
• Age 45-80 years, with > 10 years life expectancy.
• Biopsy-confirmed, NCCN (favorable GG2 and unfavorable GG3) intermediate-risk prostate cancer.
• Stage ≤ T2c, N0, M0.
• ISUP Grade Group 2 or 3 disease on TRUS-guided biopsy (minimum 8 cores, combination of systematic and MRI fusion-guided) or in-bore biopsy (minimum 3 cores from each PI-RADS v2 category ≥ 3 lesion). Biopsy reported within 12 months of baseline visit, with minimum 6-week interval between biopsy and baseline.
• PSA ≤ 20 ng/mL reported within 3 months of baseline.
• Treatment naïve.
• Planned ablation volume < 3.0 cm axial radius from the urethra on mpMRI acquired within 6 months of baseline.  

• Inability to undergo MRI or general anaesthesia.
• Suspected tumour > 30 mm from the prostatic urethra.
• Prostate calcifications > 3 mm in maximum extent obstructing ablation of tumour on low-dose pelvic CT:                
  • Criteria subject to additional review and approval by sponsor. Alternatively, prospective TRUS to query calcifications or susceptibility-weighted MRI if available may be used to assess calcifications. Imaging for calcification screening must be dated within 1 year of baseline visit.
• Unresolved urinary tract infection or prostatitis.
• History of proctitis, bladder stones, hematuria, history of acute urinary retention, severe neurogenic bladder.
• Artificial urinary sphincter, penile implant or intraprostatic implant.
• Less than 10 years life expectancy.
• Patients who are otherwise not deemed candidates for RP.
• Inability or unwillingness to provide informed consent.
• History of anal or rectal fibrosis or stenosis, or urethral stenosis, or other abnormality challenging insertion of devices.

Eligibility last updated 2/7/22. Questions regarding updates should be directed to the study team contact.

• Deceased children with partial ornithine transcarbamylase (OTC) deficiency who were under strict treatment and died unexpectedly, and their parents.

• Lack of quality or significant volume of DNA from all submitted specimens.

Eligibility last updated 2/3/22. Questions regarding updates should be directed to the study team contact.

• Has a histologically or cytologically confirmed diagnosis of Stage IV (T any, N any, M1a, M1b, M1c
  •AJCC eighth Edition) squamous or nonsquamous NSCLC.
  • Note: Mixed tumors will be characterized by the predominant cell type; if small cell elements are present, the participant is ineligible.
• Has measurable disease based on RECIST 1.1, as determined by the local site assessment.
  • Note: Measurable disease is defined as having at least 1 measurable lesion by CT or MRI per RECIST 1.1. Lesions that appear measurable but are situated in a previously irradiated area can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
• Has provided tumor tissue (post diagnosis of metastatic disease is preferred) for determination of PD-L1 status before randomization.
  • Note: Assessment of PD-L1 expression must be made from provided archival tumor tissue sample or newly obtained core or incisional or excisional biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are preferred to slides. Details pertaining to tumor tissue submission can be found in the Laboratory Manual.
• Has confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of the absence of tumor-activating EGFR mutations [e.g., DEL19 or L858R], AND absence of ALK and ROS1 gene rearrangements).
  • Note: If participant’s tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation and ALK and ROS1 translocations will not be required, as this is not part of current diagnostic guidelines.
• Has not received prior systemic treatment for metastatic NSCLC.
• Is male or female, from ≥ 18 years of age inclusive, at the time of signing the informed consent.
• Has an ECOG PS of 0 or 1 assessed within 7 days before randomization.
• Has a life expectancy of at least 3 months.
• If male, agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows:
  • Chemotherapy: at least 95 days from the last dose;
  • Refrain from donating sperm; PLUS either:
  • Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent; OR
  • Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview as detailed below:
  • Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
  • Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penilevaginal penetration.
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
• A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies:
  • Not a WOCBP; OR
  • Is a WOCBP and:
  • Uses a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:
    • MK-7684A/pembrolizumab: 120 days;
    • Chemotherapy: 180 days.
• The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
• Has a negative highly sensitive pregnancy test ( as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. 
• Abstains from breastfeeding during the study intervention period and for at least 120 days after the last dose of study intervention.
• Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy. 
• The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. The participant may also provide consent/assent for FBR.  However, the participant may participate in the study without participating in FBR.
• Has adequate organ function. Specimens must be collected within 10 days before the start of study intervention.
• Absolute neutrophil count (ANC) ≥ 1500/μL.
• Platelets ≥ 100 000/μL.
• Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/La.
• Estimated creatinine clearance using the Cockcroft-Gault equation.
• To initiate treatment with carboplatin or cisplatin, CrCl must be ≥ 60 mL/min
• Total bilirubin ≤ 1.5 ×ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN.
• AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases).
• International normalized ratio (INR) OR prothrombin time (PT).
• Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Abbreviations: ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); ANC=absolute neutrophil count; AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
• Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Estimated creatinine clearance using Cockcroft-Gault:
  • (140-age [years] × weight (kg) (×F)*Serum creatinine (mg/dL) × 72 *where F = 0.85 for females and F = 1 for males
  • Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements are to be adapted according to local regulations and guidelines for the administration of specific chemotherapies.

• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (i.e., without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention.
• Participants with asymptomatic brain metastases (i.e., no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm) may participate.
• Severe hypersensitivity (≥ Grade 3) to MK-7684, MK-7684A, pembrolizumab, chemotherapy components, and/or any of its excipients.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study medication.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).  Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Note: Lymphangitic spread of the NSCLC is not exclusionary.
• Active infection requiring systemic therapy.
• Known history of HIV infection. No HIV testing is required unless mandated by local health authority.
• Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• History or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
• Received prior therapy with an anti-TIGIT, anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Received prior systemic anticancer therapy for metastatic disease.
  • Note: Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months before the development of metastatic disease.
• If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention.
• Received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis. 
  • Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
• Received radiation therapy to the lung that is > 30 Gray within 6 months of the first dose of study intervention.
• Received a live or live attenuated vaccine within 30 days before the first dose of study
• intervention. Administration of killed vaccines are allowed. 
• Is unable to interrupt aspirin or other NSAIDs, other than an aspirin dose ≤ 1.3 g/day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
• Is unable or unwilling to take folic acid or vitamin B12 supplementation.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
  • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• History of allogenic tissue/solid organ transplant.

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

• Diagnosis of seropositive rheumatoid arthritis (either Rheumatoid factor or anti-CCP positive).
• Age-matched Healthy Controls.

• Chronic active viral infection.
• History of chemo/radiotherapy.
• History of cancer.
• Other autoimmune disease.
• Pregnancy.

Eligibility last updated 3/23/22. Questions regarding updates should be directed to the study team contact.

• Have completed a Corcept-sponsored study of relacorilant in endogenous Cushing syndrome with at least 80% compliance with the dosing schedule.
• According to the Investigator's opinion, will benefit from continuing treatment with relacorilant.

• Premature discontinuation from a relacorilant parent study.
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism.
• Has poorly controlled hypertension.
• Has Stage ≥ 4 renal failure.

Eligibility last updated 2/8/22. Questions regarding updates should be directed to the study team contact.

• Male and female patients aged ≥ 18 years at the time of informed consent form (ICF) signature.
• Received allogeneic HSCT from a related or unrelated, human leukocyte antigen-matched or mismatched donor. Patients having received any of the following stem cell sources are eligible: granulocyte colony stimulating factor mobilized peripheral blood stem cells, bone marrow, umbilical cord blood.
• Diagnosis of TA-TMA established by histologic evidence of microangiopathy in any biopsied organ OR, as per the laboratory markers below, indicating TMA:
  • De novo or progressing thrombocytopenia (platelet count < 50 x 10^9/L or > 50 % decrease in platelet count from the highest value achieved after transplantation); AND
  • Elevated LDH (> 1.5 x ULN); AND
  • At least 1 additional laboratory criteria among the following:
  • Schistocytes on the peripheral blood smear (≥ 2 per hpf); OR
  • De novo anemia (hemoglobin < LLN or anemia requiring PRBC transfusion support as per local institutional standard); OR
  • Proteinuria (rUPCR ≥ 2 mg/mg); OR
  • Elevated plasma concentration of sC5b-9 above ULN.
• Have a diagnosis of TA-TMA that persists despite initial management of any triggering condition.
• Have at least 1 sign/symptom of organ dysfunction:
  • Kidney: doubling of serum creatinine compared with pre-HSCT level or patient receiving renal replacement therapy or proteinuria ≥ 30 mg/dL AND rUPCR ≥ 2 mg/mg;
  • Lungs: hypoxemia or any need for noninvasive or invasive positive pressure ventilation;
  • Cardiovascular: pulmonary hypertension diagnosed by a cardiologist using cardiac catheterization, or pulmonary hypertension criteria on echocardiography or arterial hypertension, defined by systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg at baseline or hypertension requiring > 2 medications (excluding diuretics);
  • Serositis: clinically significant pleural effusion or pericardial effusion requiring surgical therapy (e.g., pericardiocentesis/ thoracocentesis);
  • CNS: seizures attributable to posterior reversible encephalopathy syndrome;
  • GI tract: presence of biopsy-proven GI TA-TMA. Patients with GI bleeding (hematemesis or hematochezia) will be excluded.
• Women of childbearing potential, defined as any women who have experienced menarche and who are NOT permanently sterile or postmenopausal, must have a negative serum pregnancy test at screening and agree to use protocol-defined methods of contraception for the duration of the study and 8 weeks after their last IMP dose.
  • Note: Postmenopausal is defined as having had 12 consecutive months with no menses without an alternative medical cause.
• Men must agree to the following for the duration of the study and 8 weeks after their last dose of IMP:
  • Avoid fathering a child;
  • Use protocol-defined methods of contraception;
  • Refrain from donating sperm.
• Patient and/or legally authorized representative must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.

• Positive direct Coombs test.
• Known familial or acquired ADAMTS13 deficiency.
• Known Shiga toxin‐related hemolytic uremic syndrome.
• Known bone marrow or graft failure.
• Diagnosis of disseminated intravascular coagulation.
• Diagnosis of VOD.
• Active GI bleeding (hematemesis or hematochezia) at baseline.
• Body weight < 30 kg and > 100 kg.
• Uncontrolled systemic bacterial or fungal infection, presence or suspicion of sepsis.
• Previously or currently treated with a complement inhibitor (approved or investigational).
• Pregnancy or breastfeeding.
• Positive human immunodeficiency virus antibody at screening or documented in pre-HSCT medical record.
• Hepatitis C virus detectable by polymerase chain reaction at screening or documented in pre-HSCT medical record.
• Chronic inactive hepatitis B virus with viral loads > 1000 IU/mL (> 5000 copies/mL) at screening or documented in pre-HSCT medical record. Eligible patients who are chronic active carriers (≤ 1000 IU/mL) must receive prophylactic antiviral treatment (e.g., entecavir, tenofovir, lamivudine) according to local country guidelines.
• Inability to cooperate with study procedures or any condition that, in the opinion of the investigator, could increase the patient’s risk by participating in the study or confound the outcome of the study.

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

• Women who will give birth at Mayo Clinic by caesarean-section at term following an uncomplicated pregnancy.

• Multiple pregnancy.
• Known presence of clinical infections (e.g., chorioamnionitis), congenital anomalies or maternal pathologies (i.e., diabetes, hypertension, preeclampsia).
• Intrauterine growth retardation or fetal macrosomia.
• Maternal age under 18 or over 50.
• Maternal body mass index (BMI) of less than 18 and more than 40.
• Pregnancy less than 37 weeks of completed gestation.

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

• Age 22
  •65 years.
• BMI ≥ 35 and < 40 kg/m^2 or BMI of 30 to 34.9 kg/m^2 with one or more major obesity-related comorbid conditions.
• Willingness to comply with the substantial lifelong dietary restrictions required by the procedure.
• History of obesity (BMI ≥ 30) for at least 2 years.
• History of failure with non-surgical weight loss methods.
• Willingness to follow protocol requirements, including signed informed consent, routine follow-up schedule, completing laboratory tests, completing diet counseling.
• Residing within a reasonable distance from the investigator’s office and able to travel to the investigator to complete all routine follow-up visits.
• Ability to give informed consent.
• Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must agree to use adequate birth control methods.  Acceptable birth control methods are limited to hormonal contraceptives (oral, flexible vaginal ring, skin patch, injection), diaphragms, IUDs, condoms with or without spermicide, and voluntary abstinence.  Should a treatment arm subject become pregnant during the implantation period, the balloon will be extracted during the second trimester
  •the timing of which will be determined via consultation with the subject’s obstetrician.

• Prior surgery involving the esophagus, stomach, and duodenum or bariatric surgery.
• Prior open or laparoscopic bariatric surgery.
• Prior surgery of any kind on the esophagus, stomach, duodenum or any type of hiatal hernia surgery.
• Any inflammatory disease of the gastrointestinal tract including esophagitis, Barrett’s esophagus, gastric ulceration, duodenal ulceration, cancer or specific inflammation such as Crohn’s disease
• Potential upper gastrointestinal bleeding conditions such as esophageal or gastric varices, congenital or acquired intestinal telangiectasis, or other congenital anomalies of the gastrointestinal tract such as atresias or stenoses.
• A gastric mass.
• A hiatal hernia > 2cm or severe or intractable gastro-esophageal reflux symptoms.
• Acid reflux symptoms to any degree that require more than one medication for symptom control.
• A structural abnormality in the esophagus or pharynx such as a stricture or diverticulum that could impede passage of the balloon alongside the endoscope.
• Achalasia or any other severe esophageal motility disorder that may pose a safety risk during the removal of the device.
• Severe coagulopathy.
• Insulin-dependent diabetes (either Type 1 or Type 2) or a significant likelihood of requiring insulin treatment in the following 12 months.
• Subjects with any serious health condition unrelated to their weight that would increase the risk of endoscopy.
• Chronic abdominal pain.
• Motility disorders of the GI tract such as gross esophageal motility disorders, gastroparesis or intractable constipation.
• Hepatic insufficiency or cirrhosis.
• Serious or uncontrolled psychiatric illness or disorder that could compromise patient understanding of or compliance with follow up visits and removal of the device after 8 months.
• Alcoholism or drug addiction.
• Patients unwilling to participate in an established medically-supervised diet and behavior modification program, with routine medical follow-up.
• Patients receiving daily prescribed treatment with aspirin, anti-inflammatory agents, anticoagulants or other gastric irritants.
• Patients who are unable or unwilling to take prescribed proton pump inhibitor medication for the duration of the device implant.
• Patients who are known to have, or suspected to have, an allergic reaction to materials contained in the system.
• Patients who have BOTH:
  • A previous history of a serotonin syndrome; AND
• • currently taking any drug known to affect the levels of serotonin in the body [e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs)].
• Patients who are pregnant or breast-feeding.
• Subjects with severe cardiopulmonary disease or other serious organic disease which might include known history of coronary artery disease, myocardial infarction within the past 6 months, poorly controlled hypertension, required use of NSAIDs.
• Subjects who have tested positive for H. Pylori, and who have not yet been treated.

Eligibility last updated 2/3/22. Questions regarding updates should be directed to the study team contact.

• Males and females ≥ 18 years of age
• Have locally advanced or metastatic solid tumor malignancy with measurable disease and be an appropriate candidate for experimental therapy.
• Part A (JSI-1187 Monotherapy Dose Escalation):
  • Histologically or cytologically confirmed MAPK pathway mutation, including hyperactivating pathway mutations or gene fusions; e.g., BRAF (Class I, II or III), RAS (H/K/N), MEK (MAP2K1), RAS-GAP (NF1 loss, RASA1), RAS-GEF, refractory to or relapsed on prior therapy, and have received all available therapy known to confer clinical benefit.
  • Part B (JSI-1187 Plus Dabrafenib Combination Dose Escalation):
    • Histologically or cytologically confirmed BRAF V600-mutated locally advanced or metastatic solid tumor, refractory to, or relapsed on, prior therapy, and have received all available therapy known to confer clinical benefit.
• Part C (JSI-1187 Plus Dabrafenib Expansion Cohorts): Histologically or cytologically confirmed:
  • Cohort 1: BRAF V600-mutated metastatic melanoma after two prior therapies for metastatic disease, including anti-PD1 therapy, with or without ipilimumab, and BRAF/MEK inhibitor treatment;
  • Cohort 2: BRAF V600-mutated metastatic melanoma after adjuvant therapy for Stage 3 disease followed by one prior therapy for metastatic disease, including anti-PD-1 therapy, with or without ipilimumab or BRAF/MEK inhibitor treatment;
  • Cohort 3: Either BRAF V600E-mutated metastatic non-small cell lung cancer (NSCLC), or BRAF V600-mutated metastatic solid tumor, after 1 or 2 prior therapies.
• MAPK mutation tumor status will be established prior to entry based on previous MAPK pathway mutation reports from a CLIA qualified laboratory, or, if a report is not available, the mutation analysis will be performed at Screening on archival tissue or newly biopsied tumor tissue.
• Have discontinued previous treatments for cancer and have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior chemotherapy, surgery, or radiotherapy to Grade ≤ 1.
• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2.
• Life expectancy of ≥ 3 months -Subjects with asymptomatic stable, prior or currently treated brain metastases are allowed -Adequate hematologic parameters without ongoing transfusional support:
  • Hemoglobin (Hb) ≥ 9 g/dL -Absolute neutrophil count (ANC) ≥ 1.0 x 10^9 cells/L;
  • Platelets ≥ 75 x 10^9 cells/L -Adequate renal and hepatic function;
  • Creatinine ≤ 1.5 times the upper limit of normal (ULN), or calculated creatinine clearance ≥ 50 mL/minute x 1.73 m^2 per the Cockcroft-Gault formula;
  • Total bilirubin ≤ 2 times the (ULN) unless due to Gilbert's disease;
  • ALT/AST ≤ 2.5 times the ULN, or < 5 times the ULN for subjects with liver metastases.
• Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy throughout the study and for 28 days after the completion of study treatment.
• Ability to provide written informed consent.

• Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV.
• QT interval corrected for rate (QTc) > 480 msec on the ECG obtained at Screening using Fridericia method for QTc calculation.
• Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, with the exception of anti-microbials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for patient care.
• Medications that are strong inhibitors of CYP3A4 are prohibited during study and for 14 days prior to the first dose of study drug(s).
• Medications that are strong inducers of CYP3A4 are prohibited during study and for 14 days prior to the first dose of study drug(s).
• Medications that are strong inhibitors of BCRP are prohibited during study and for 14 days prior to the first dose of study drugs(s).
• Subjects on dabrafenib (Parts B and C) also are advised to avoid concurrent administration of strong inhibitors of CYP2C8 as these medications may increase the concentration of dabrafenib -History of or current evidence/risk of retinal vein occlusion or central serous retinopathy, or has medically relevant abnormalities identified on screening ophthalmologic examination -Symptomatic central nervous system malignancy or metastasis -Gastrointestinal conditions that could impair absorption of study drug(s).
• Current hematologic malignancies -Second, active primary solid tumor malignancy that, in the judgement of the investigator or Sponsor medical monitor, may affect the interpretation of results.
• Prior malignancies, with the exception of carcinoma in situ of any origin, non-muscle invasive bladder cancer, Gleason 3+3 prostate cancer and prior malignancies in remission whose likelihood of recurrence is very low, as judged by the Sponsor medical monitor.
• Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment within the last week prior to study treatment.
• Other active infection requiring IV antibiotic usage within the last week prior to study treatment.
• Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results.
• Participation within the last 28 days in a clinical trial, or currently enrolled in a clinical trial, involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
• Previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor.
• If female, pregnant, breast-feeding, or planning to become pregnant.

Eligibility last updated 2/24/22. Questions regarding updates should be directed to the study team contact.

• Males and females between 18 and 85 years of age, inclusive, at screening.
• Body mass index < 35 kg/m^2.
• Diagnosed with HCM per the following criteria:
  • Has LV hypertrophy and non-dilated LV chamber in the absence of other cardiac disease; and 
  • Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory of:
    • ≥ 15 mm in one or more myocardial segments; OR
    • ≥ 13 mm in one or more wall segments and a known-disease-causing gene mutation or positive family history of HCM.
• Has resting LVOT-G ≥ 30 mmHg and post-Valsalva LVOT G ≥ 50 mmHg during screening as determined by the echocardiography core laboratory.
• LVEF ≥ 60% at screening as determined by the echocardiography core laboratory.
• NYHA Functional Class II or III at screening.
• Hemoglobin ≥ 10g/dL at screening.
• Respiratory exchange ratio (RER) ≥ 1.05 and pVO2 < 80% predicted on the screening CPET per the core laboratory.
• Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been on stable doses for > 6 weeks prior to randomization and anticipate remaining on the same medication regimen during the trial. Patients treated with disopyramide must also be concomitantly treated with a beta blocker and/or calcium channel blocker.

• Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (e.g., Noonan syndrome, Fabry disease, amyloidosis).
• Significant valvular heart disease (per investigator judgment).
• Moderate-severe valvular aortic stenosis.
• Moderate-severe mitral regurgitation not due to systolic anterior motion of the mitral valve.
• History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any time during their clinical course.
• Inability to exercise on a treadmill or bicycle (e.g., orthopedic limitations).
• Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or has plans for either treatment during the trial period.
• Documented paroxysmal atrial fibrillation during the screening period.
• Paroxysmal or permanent atrial fibrillation requiring rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) ≤ 6 months prior to screening. (This exclusion does not apply if atrial fibrillation has been treated with anticoagulation and adequately rate-controlled for > 6 months).
• History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening.
• Has received prior treatment with CK-3773274 or mavacamten.

Eligibility last updated 2/24/22. Questions regarding updates should be directed to the study team contact.

• Men and women ≥ 50 years of age.
• The patient has met eligibility criteria and is planned to undergo LAAO with the WATCHMAN FLX device as part of clinical care.
• The patient is able and willing to undergo non-invasive cognitive testing using the Viewmind headset by a trained personal.
• The patient is able to give informed consent for the procedure.

• The patient unwilling or unable to complete cognitive testing using the specialized virtual reality googles.
• Primary language is not English.

Eligibility last updated 3/11/22. Questions regarding updates should be directed to the study team contact.

• Adult (18 years or older).
• Able to provide informed consent 
• Able to provide samples in English.
• U.S. based patient.

• Age < 18 years of age.
• Unable to provide samples in English (i.e., need for interpreter flag in Epic).
• Nonverbal / No speech.
• HPP (High Profile Patient) status.
• International patient.

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

Inclusion Criteria
•Main Phase 0:

• Histologically (if prior biopsy) or radiologically diagnosed glioblastoma.
• Eligible for neurosurgical tumor resection.
• Patients must be at least 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate organ function.
• Life expectancy ≥ 3 months at the start of treatment in the opinion of the investigator.

Inclusion Criteria
•Main Phase Ia:

• Histologically demonstrated diagnosis of TP53 wild type glioblastoma harboring unmethylated MGMT promoters (Glioblastoma definition according to 2021 WHO Classification of CNS tumors; i.e., IDH-wild type only).
• Patient has undergone neurosurgical tumor resection and is eligible for standard radiotherapy.
• Formalin-fixed paraffin-embedded tumor blocks or representative H/E (haematoxylin/eosin) slides (preferably both) must be available for retrospective histopathological central review.
• Locally performed histopathological diagnosis will be accepted for entry into this trial.
• Patients must be at least 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate organ function.
• Life expectancy ≥ 3 months at the start of treatment in the opinion of the investigator.

Exclusion Criteria
•Main Phase 0:

• Known TP53 mutant glioblastoma.
  • Note: testing is not mandatory for inclusion.
• Known IDH mutant grade IV astrocytoma.
  • Note: testing is not mandatory for inclusion.
• Patients with pacemakers or other metallic implants that can interfere with the magnetic field during MRI investigations.
• Inability to undergo contrast-enhanced MRI (GFR < 30 mL/min).

Exclusion Criteria
•Main Phase Ia:

• Patients who have received previous systemic therapy (with the exception of patients who participated in Phase 0) or radiotherapy for glioblastoma.
• Patients with pacemakers or other metallic implants that can interfere with the magnetic field during MRI investigations.
• Inability to undergo contrast-enhanced MRI (GFR < 30 mL/min).

Eligibility last updated 3/1/22. Questions regarding updates should be directed to the study team contact.

• Subject is older than 18 years of age.
• Symptomatic coronary artery disease (CAD) with greater than or equal to 90 days of persistent refractory angina pectoris classified as CCS Grade III or IV despite maximally tolerated guideline directed medical therapy.
• Must have attempted treatment with the maximally tolerated dose of at least three of the four (and preferably all four) approved classes of anti-anginal agents:
  • long-acting nitrates, calcium channel blockers (either a dihydropyridine or a non-dihydropyridine), beta blockers, and ranolazine. The regimen must be stable for greater than 2 months prior to enrollment, with no intent to change the medical regimen for at least 12 months after randomization.
• Subject has either no treatment options for revascularization by coronary artery bypass grafting or by percutaneous coronary intervention, or is otherwise unsuitable or high risk for revascularization.
• Evidence of either exercise or pharmacologically induced reversible ischemia severity by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, FFRCT, FFR, iFR, or other non-hyperemic FDA approved tests in the distribution of the left coronary artery (LCA). Note: if the subject has evidence of ischemia in both the LCA and RCA distributions, the extent of ischemia must be greater in the LCA distribution.
• Functional limitation due to refractory angina as defined by a modified Bruce exercise tolerance test duration of greater than or equal to 2 minutes but less than or equal to 8 minutes:
  • Subject has ETT variability less than 20% between last two ETTs performed.
• Left ventricular ejection fraction (LVEF) greater than or equal to 30% within the 12-months prior to procedure (must be reassessed after any intervening myocardial infarction); the most recent LVEF assessment is used as the qualifying test.
• Subject is willing and able to sign informed consent.
• Subject is willing to comply with the specified follow-up evaluations.

• Recent (within 30 days prior to enrollment) troponin or CKMB positive acute coronary syndrome (NSTEMI or STEMI).
• Recent successful revascularization by CABG or PCI within six months prior to enrollment.
• Recent unsuccessful PCI (e.g., no relief from symptoms, failed attempt to open a chronic total occlusion) within 30 days prior to enrollment.
• The predominant manifestation of angina is dyspnea .
• Has extra-coronary contributory causes of angina; e.g., untreated hyperthyroidism, anemia (hgb < 10 g/dL), uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg despite medications), atrial fibrillation with rapid ventricular response (consistently >100 bpm despite medications) or other tachyarrhythmia, severe aortic stenosis, hypertrophic cardiomyopathy with left ventricular outflow tract obstruction or asymmetric septal hypertrophy (concentric left ventricular hypertrophy is not an exclusion criterion), etc.
• NYHA Class III or IV heart failure (HF), decompensated HF or hospitalization due to HF during the 90 days prior to enrollment.
• Life threatening rhythm disorders or any rhythm disorders that would require future placement of an internal defibrillator and/or pacemaker.
• Severe chronic obstructive pulmonary disease (COPD) as indicated by a forced expiratory volume in one second (FEV1) that is less than 55% of the predicted value, or need for home daytime oxygen or oral steroids.
• Severe valvular heart disease (any valve).
• Moderate or severe RV dysfunction by echocardiography.
• Pacemaker electrode/lead is present in the coronary sinus.
• A Class I indication is present for an implantable defibrillator or cardiac resynchronization therapy according to ACCF/AHA/HRS guidelines.
• Recent implantation of a new pacemaker or defibrillator lead with electrode in the right atrium within 90 days of enrollment.
• Chronic severe renal failure (estimated eGFR less than 30 mL/min/1.73m2 by the MDRD formula) or subjects on chronic dialysis.
• Known allergy to stainless steel or nickel.
• Any clinical condition that might interfere with the trial protocol or the subject's ability to be compliant with the trial protocol (e.g., active alcohol or drug abuse, dementia, magnetic resonances imaging (MRI) planned within 8 weeks of randomization, etc.).
• Currently enrolled in another investigational device or drug trial that has not reached its primary endpoint or that might clinically interfere with the current trial endpoints or procedures.
• Pregnant or planning pregnancy within the next 12 months (women of reproductive potential must have a negative pregnancy test within 7 days of the randomization procedure).
• Subject is part of a vulnerable population who, in the judgment of the investigator, is unable to give Informed Consent for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy. This may include individuals with mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention.
• Inability to tolerate dual antiplatelet therapy for 6 months if not on a chronic oral anticoagulant, or inability to tolerate a P2Y12 inhibitor for at least 6 months if on a chronic oral anticoagulant.
• Comorbidities limiting life expectancy to less than one year.

Eligibility last updated 4/15/22. Questions regarding updates should be directed to the study team contact.

• Adult postmenopausal women, aged 45-60 years.
• Menopause symptoms (hot flashes/night sweats) rated moderate or greater or total MRS score ≥ 14.

• Current use of hormone therapy.

Eligibility last updated 3/10/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 7/14/22. Questions regarding updates should be directed to the study team contact.

• Any patient undergoing surgery for intralesional resection of neoplasm such as tumors of the spine/extremities or metastatic disease.

• Patients undergoing surgery with an expected blood loss of less than 135cc.
• Provisions for inclusion of minorities: 
  • Subjects will be enrolled prospectively irrespective of their sex/gender, race, and ethnicity in order to improve generalizability.        

Eligibility last updated 2/21/22. Questions regarding updates should be directed to the study team contact.

• Age 21-65.
• BMI ≥ 30 and ≤ 40 kg/m² .
• Willingness to comply with the substantial lifelong dietary restrictions required by the procedure.
• History of failure with non-surgical weight-loss methods.
• Willingness to follow protocol requirements, including signed informed consent, routine follow-up schedule, completing laboratory tests, and completing diet counseling. 
• Residing within a reasonable distance from the investigator’s office and able to travel to the investigator to complete all routine follow- up visits.
• Ability to give informed consent.
• Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must agree to use adequate birth control methods. 

• History of foregut or gastrointestinal (GI) surgery (except uncomplicated cholecystectomy or appendectomy).
• Prior gastrointestinal surgery with sequelae; i.e., obstruction, and/or adhesive peritonitis or known abdominal adhesions.  
• Prior open or laparoscopic bariatric surgery.  
• Prior surgery of any kind on the esophagus, stomach or any type of hiatal hernia surgery. 
• Any inflammatory disease of the gastrointestinal tract including severe (LA Grade C or D) esophagitis, Barrett’s esophagus, gastric ulceration, duodenal ulceration, cancer or specific inflammation such as Crohn’s disease.  
• Potential upper gastrointestinal bleeding conditions such as esophageal or gastric varices, congenital or acquired intestinal telangiectasis, or other congenital anomalies of the gastrointestinal tract such as atresias or stenoses. 
• Gastrointestinal stromal tumors, history of premalignant gastric lesions (intestinal metaplasia), history of familial and nan-familial adenomatous syndromes.  
• A gastric mass or gastric polyps > 1 cm in size.  
• A hiatal hernia > 4cm of axial displacement of the z-line above the diaphragm or severe or intractable gastro-esophageal reflux symptoms.  
• A structural abnormality in the esophagus or pharynx such as a stricture or diverticulum that could impede passage of the endoscope.  
• Achalasia or any other severe esophageal motility disorder.
• Severe coagulopathy. 
• Insulin-dependent diabetes (either Type 1 or Type 2) or a significant likelihood of requiring insulin treatment in the following 12 months or a HgbA1C ≥ 9. 
• Subjects with any serious health condition unrelated to their weight that would increase the risk of endoscopy.
• Chronic abdominal pain.
• Motility disorders of the GI tract such as gross esophageal motility disorders, gastroparesis or intractable constipation. 
• Hepatic insufficiency or cirrhosis.
• Use of an intragastric device prior to this study due to the increased thickness of the stomach wall preventing effective suturing.  
• Active psychological issues preventing participation in a life-style modification program as determined by a psychologist.
• Patients unwilling to participate in an established medically supervised diet and behavior modification program, with routine medical follow-up.  
• Patients receiving daily prescribed treatment with high dose aspirin (> 80 mg daily), anti-inflammatory agents, anticoagulants or other gastric irritants.  
• Patients who are unable or unwilling to take prescribed proton pump inhibitor medication.
• Patients who are pregnant or breast-feeding.  
• Patients currently taking weight-loss medications or other therapies for weight loss within the prior 6 months. 
• Subjects with severe cardiopulmonary disease or other serious organic disease which might include known history of coronary artery disease, myocardial infarction within the past 6 months, poorly controlled hypertension, required use of NSAIDs.
• Subjects taking medications on specified hourly intervals that may be affected by changes to gastric emptying, such as anti-seizure or anti-arrhythmic medications.
• Subjects who are taking corticosteroids, immunosuppressants, and narcotics.
• Symptomatic congestive heart failure, cardiac arrhythmia or unstable coronary artery disease.  
• Pre-existing respiratory disease such as moderate or severe chronic obstructive pulmonary disease (COPD) requiring steroids, pneumonia or cancer.  
• Diagnosis of autoimmune connective tissue disorder (e.g. lupus, erythematous, scleroderma) or immunocompromised.  
• Specific diagnosed genetic disorder such as Prader Willi syndrome. 
• Eating disorders including night eating syndrome (NES), bulimia, binge eating disorder, or compulsive overeating. 
• Known history of endocrine disorders affecting weight such as uncontrolled hypothyroidism. 
• If deemed medically inappropriate or ineligible by investigator. 

Eligibility last updated 2/1/22. Questions regarding updates should be directed to the study team contact.

• Patients referred to the Mayo Clinic HF Clinic with a diagnosis of heart failure who have a clinical blood draw scheduled.
• Adults ≥ 18 years old.

• Individuals < 18 years old.
• Any history of Hemoglobin less than 9 mg/dL during the past 3 months.
• Active cancer.

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

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

Eligibility last updated 2/8/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 10/18/22. Questions regarding updates should be directed to the study team contact.

• Centrally confirmed HER2+ breast carcinoma per 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines.
• Have unresectable locally advanced or metastatic disease.
• If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab or pertuzumab received for advanced HER2+ disease.
• Have received 4-8 cycles (21 day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression.
• Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-]).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 -CNS Inclusion.
•  Based on screening contrast brain magnetic resonance imaging (MRI), participants may have any of the following:
  • No evidence of brain metastases;
  • Untreated brain metastases which are asymptomatic and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane;
  • Previously treated brain metastases which are asymptomatic;
  • Brain metastases previously treated with local therapy must not have progressed since treatment.

• Prior treatment with any anti-HER2 and/or anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug).
• Unable to undergo contrast MRI of the brain -

CNS Exclusion:

• Based on screening brain MRI and clinical assessment.
• Symptomatic brain metastasis.
• Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane.
• Ongoing use of systemic corticosteroids at a total daily dose of > 2 mg of dexamethasone (or equivalent).
• Any untreated brain lesion in an anatomic site which may pose risk to participant.
• Known or suspected leptomeningeal disease (LMD).
• Poorly controlled (> 1/week) seizures, or other persistent neurologic symptoms.

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

• Patients with life or limb threatening traumatic injury to an arterial vessel in the limb or torso, other than the heart, which requires replacement or reconstruction.
• Preoperative imaging or clinical examination indicates the damaged vessel has a defect length of ≤ 38cm and is appropriately size matched to the 6mm Human Acellular Vessel (HAV) per the judgment of the treating surgeon taking into account vasoconstriction and situational inflow and outflow considerations.
• Autologous vein graft is either not feasible in the judgment of the treating surgeon (e.g., because of lack of availability of suitable conduit, presence of severe venous insufficiency) or is not desirable because of the urgency of revascularization.
• Aged 18 to 85 years old, inclusive.
• Able to communicate meaningfully with investigative staff, and able to comply with entire study procedures. If the patient is unconscious, then information from a reliable witness indicates that the patient would normally be able to comply with study procedures.
• Patient or relative is able, willing and competent to give informed consent.
• Life expectancy of at least 1 year.

• Mangled Extremity Severity Score (MESS) of ≥ 7.
• Limb at high risk of amputation despite vascular reconstruction (e.g., because of crush injury).
• Catastrophic injuries that make survival unlikely (e.g., Abbreviated Injury Scale (AIS) > 5 or Injury Severity Score (ISS) > 60).
• HAV may not be used for coronary artery repair.
• Known pregnant women.
• Known medical condition which would preclude long term antiplatelet therapy after resolution of acute injuries.
• Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAV.
• Previous exposure to HAV.
• Known participation in any investigational study within the last 30 days.
• Employees of the sponsor or patients who are employees or relatives of the investigator.

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

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

Eligibility last updated 1/18/23. Questions regarding updates should be directed to the study team contact.

• Patient must be ≥ 18 years and ≤ 39 years of age at registration.
• Patient must have a histologically confirmed diagnosis of primary cancer of any stage within 12 weeks (84 days) at registration.
• Patient must have received, be currently receiving or planning to receive treatment for cancer, including surgery and/or chemotherapy and/or radiation therapy.
• Patient must have an ECOG performance status 0-3.
• Patient must have a life expectancy > 24 months.
• Patient must be able to complete questionnaires in English.
• Patient must have internet access through computer, tablet, or smartphone.
• Patient must have an email address.
• Patient must have a mobile phone able with text messaging capabilities.
• Patient must be able to accurately provide self-report data (e.g., per clinical judgment, cognitive function is intact). Patient must be able to provide informed consent.

• Patient must not have a recurrence or second primary cancer.
• Patient must not have basal cell skin carcinoma.

Eligibility last updated 2/17/22. Questions regarding updates should be directed to the study team contact.

• Male and female, age 18 and older.
• Suspected of having eye tumor.

AIM 1 - SUBSET OF LARGE CHOROIDAL NEVI:

• Lesions with thickness > 1.5 mm and minimum documented stability interval of 2 years.

• Lesions with thickness < 1.5 mm or fewer than 2 years of documented stability.

SUBSET LARGE MELANOMA:

• Choroidal, ciliary body, or ciliochoroidal melanoma in a patient who elected to have enucleation for primary tumor treatment.

• Iris melanoma or melanoma that has undergone prior treatment before enucleation.

PRESUMED CHOROIDAL MELANOMA:

•  Choroidal, ciliary body, or ciliochoroidal melanoma with thickness > 1.5 mm treated by radiation. These lesions may sometimes have biopsy for cytogenetic testing at the time of radiation treatment.

• Iris melanoma, lesions with thickness < 1.5 mm, non-melanoma tumors.

AIM 2

• Orbital mass with completed neuroimaging (typically with MRI) and clinical/MRI suspicion for lymphoma.

• Recent orbital biopsy (within the past 3 months) prior to qHDMI, clinical impression clearly compatible with a non-lymphoma tumor type.

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

• Patients ≥ 18 years old
• Patients undergoing POEM for:
  • Achalasia (types I, II, and III);
  • Non-achalasia esophageal motility disorders (e.g., diffuse esophageal spasm).
• POEM performed at Mayo Clinic by providers in the Division of Gastroenterology or the Division of Thoracic Surgery.

• Patients < 18 years old.
• Patients with prior POEM performed outside of Mayo Clinic.
• Prior upper gastrointestinal surgery.
• No authorization for research participation at Mayo Clinic.
• Inability to communicate/provide history of symptoms.

Eligibility last updated 2/17/22. Questions regarding updates should be directed to the study team contact.