Patients with a history of any arterial thrombotic event within the past 6 months; this includes angina (stable or unstable), myocardial infarction (MI), transient ischemic attack (TIA), or cerebrovascular accident (CVA)Xx_NEWLINE_xXThe patient has experienced any arterial thrombotic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollmentXx_NEWLINE_xXAngina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism , pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within 6 months prior to randomization. Deep venous thrombosis within 3 months prior to randomization unrelated to a central venous catheter, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks prior to randomization. In this situation, low molecular weight heparin is preferredXx_NEWLINE_xXHistory of any of the following within the last 6 months prior to study entry:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures  \r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) \r\n* Pulmonary embolism\r\n* New York Heart Association (NYHA) class III or IV heart failure \r\n* Placement of a pacemaker for control of rhythmXx_NEWLINE_xXNo history of any prior stroke (hemorrhagic or ischemic)Xx_NEWLINE_xXSignificant cardiovascular or cerebrovascular disease including:\r\n* Uncontrolled hypertension (systolic blood pressure [SBP] >= 150; diastolic blood pressure [DBP] >= 90)\r\n* History of myocardial infarction within 6 months\r\n* Unstable angina\r\n* New York Heart Association functional classification II, III or IV\r\n* Baseline ejection fraction =< 50% as assessed by echocardiogram or multi-gated acquisition (MUGA)\r\n* Cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 6 months\r\n* Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or peripheral arterial thrombosis) within 6 monthsXx_NEWLINE_xXPatients with a history of the following within =< 6 months of study entry are NOT eligible:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolismXx_NEWLINE_xXHistory of transient ischemic attack (TIA), cerebrovascular accident (CVA), gastrointestinal (GI) perforation or arterial thrombotic event within 6 months prior to randomization or symptomatic peripheral ischemiaXx_NEWLINE_xXA history of cardiovascular diseases: unstable angina, myocardial infarction, or known congestive heart failure class IIIV within the preceding 12 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months, pulmonary embolism within the preceding 2 monthsXx_NEWLINE_xXAngina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months.Xx_NEWLINE_xXPatients with a history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) within the past 6 months prior to study enrollment are NOT eligible for participationXx_NEWLINE_xXHistory of stroke or transient ischemic attackXx_NEWLINE_xXSubjects with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 6 monthsXx_NEWLINE_xXHistory of a major thromboembolic event =< 6 months prior to randomization, including cerebrovascular accident, transient ischemic attack (TIA), myocardial infarction, symptomatic pulmonary embolism (PE) or untreated deep venous thrombosis (DVT), or coronary artery bypass graft surgery; NOTE: Subjects with recent DVT or asymptomatic PE who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligibleXx_NEWLINE_xXHistory of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of AMG 757Xx_NEWLINE_xXHistory of arterial thrombosis (eg, stroke or transient ischemic attack) in the past 3 months.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within the previous 6 monthsXx_NEWLINE_xXHistory of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to Day 1Xx_NEWLINE_xXAny of the following cardiovascular history in the past 6 months: myocardial infarction, unstable angina, coronary/ peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, symptomatic bradycardia, requirement for anti-arrhythmic medication.Xx_NEWLINE_xXPatients who have experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollmentXx_NEWLINE_xXRecent serious cardiovascular events (within 12 months) including, but not limited to, transient ischemic attack (TIA), cerebrovascular accident (CVA), or myocardial infarction (MI).Xx_NEWLINE_xXSubjects with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or, within 6 months of the first date of treatment on this study, history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage.Xx_NEWLINE_xXAny of the following cardiovascular events within 6 months prior to study entry: myocardial infarction, malignant hypertension, severe/unstable angina, symptomatic congestive heart failure, cerebral vascular accident, or transient ischemic attackXx_NEWLINE_xXHistory of any of the following within the last 6 months prior to study registration:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure \r\n* Pulmonary embolismXx_NEWLINE_xXSubject has a history of unexplained loss of consciousness or transient ischemic attack within 12 months of treatment startXx_NEWLINE_xXClinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\r\n* Any history of myocardial infarction\r\n* Any history of clinically significant (as determined by the treating physician) atrial arrhythmia\r\n* Any history of ventricular arrhythmia\r\n* Any history of cerebrovascular accident or transient ischemic attack (TIA)\r\n* Any history of peripheral arterial occlusive disease requiring revascularization\r\n* Unstable angina within 6 months prior to enrollment\r\n* Congestive heart failure within 6 months prior to enrollment\r\n* Venous thromboembolism including deep venous thrombosis or pulmonary embolism within 6 months prior to enrollment\r\n* Unacceptable screening baseline cardiovascular assessment:\r\n** Baseline multi gated acquisition scan (MUGA) (to be done within 30 days of registration) or echocardiogram demonstrating left ventricular ejection fraction (LVEF) < 50 %\r\n** Corrected QT (QTc) >= 480 msec on screening electrocardiogram (ECG) (using the QTc Fridericia [QTcF] formula)Xx_NEWLINE_xXUncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.Xx_NEWLINE_xXHistory of arterial thrombotic disease, specifically including, but not restricted to: \r\n* Myocardial infarction or unstable angina\r\n* Cerebrovascular event (CVA) or transient ischemic attack (TIA)\r\n* Peripheral vascular disease or claudicationXx_NEWLINE_xXNo history of arterial thrombotic events such as myocardial infarction (MI), unstable angina pectoris or any ischemic or hemorrhagic cerebrovascular accident (CVA) within past 6 monthsXx_NEWLINE_xXAny of the following in the previous 6 months:\r\n* Myocardial infarction\r\n* Severe/unstable angina\r\n* Coronary/peripheral artery bypass graft\r\n* Symptomatic congestive heart failure\r\n* Cerebrovascular accident\r\n* Transient ischemic attack\r\n* Symptomatic pulmonary embolismXx_NEWLINE_xXPatients with history or evidence upon physical examination of central nervous system (CNS) disease; seizures not controlled with standard medical therapy; any brain metastases; or history of cerebral vascular accident (CVA), transient ischemic attack (TIA), or subarachnoid hemorrhage within 6 months of the first date of treatment on this study; patients diagnosed with primary brain tumors within the last three years are also excludedXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to ongoing or active infection. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.Xx_NEWLINE_xXAny of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attackXx_NEWLINE_xXHistory of any arterial thromboembolic event, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina within 6 months prior to enrollmentXx_NEWLINE_xXHave experienced any of the following within the 6-month period prior to Screening: unstable angina pectoris, clinically significant coronary artery disease, cerebrovascular accident, transient ischemic attack, cardiac failure with known ejection fraction less than 40%, or cardiac arrhythmiaXx_NEWLINE_xXHistory of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stableXx_NEWLINE_xXIschemic myocardial event, including angina requiring therapy and artery revascularization proceduresXx_NEWLINE_xXIschemic cerebrovascular event, including transient ischemic attack and artery revascularization proceduresXx_NEWLINE_xXHistory of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stableXx_NEWLINE_xXHistory of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to initiation of study treatmentXx_NEWLINE_xXNo arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible \r\n* Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this studyXx_NEWLINE_xXAny of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to registrationXx_NEWLINE_xXHistory of arterial thrombosis (eg, stroke or transient ischemic attack) in the past 3 months Infection requiring intravenous antibiotics within 1 week of study enrollment (day 1)Xx_NEWLINE_xXDiagnosis with any of the following in the 12 months prior to registration: severe/unstable angina, myocardial infarction, uncontrolled cardiac arrhythmia, congestive heart failure, cerebrovascular accident or transient ischemic attackXx_NEWLINE_xXHistory of any of the following within the last 6 months prior to study entry:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolismXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptoms.Xx_NEWLINE_xXKnown active brain or central nervous system metastasis, or seizures requiring anticonvulsant treatment, cerebrovascular accident, or transient ischemic attack (< 6 months prior to enrollment)Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to day 1Xx_NEWLINE_xXRecent (< 6 months) arterial thromboembolic events, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarctionXx_NEWLINE_xXHistory of any of the following within the last 6 months before administration of the first dose of the drug: a) Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures b) Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures c) Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) d) Placement of a pacemaker for control of rhythm e) New York Heart Association (NYHA) class III or IV heart failure f) Pulmonary embolism.Xx_NEWLINE_xXAny of the following within the 12 months prior to registration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attackXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHas had known clinically significant cardiovascular disease within 12 months of planned start of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stentXx_NEWLINE_xXHistory of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of enrollment.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months of the randomizationXx_NEWLINE_xXHistory of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to Day 1Xx_NEWLINE_xXAny of the following within 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attackXx_NEWLINE_xXSymptomatic carotid artery disease, as manifested by a recent transient ischemic attack (within 30 days), ischemic stroke, or amaurosis fugax (monocular visual ischemic symptoms or blindness).Xx_NEWLINE_xXAny of the following within 6 months before the enrollment:\r\n* Unstable angina pectoris;\r\n* Clinically-significant cardiac arrhythmias;\r\n* Stroke (including transient ischemic attack [TIA], or other ischemic event);\r\n* Myocardial infarction;\r\n* Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [eg, vena cava filter] are not eligible for this study)Xx_NEWLINE_xXIschemic myocardial event including angina requiring therapy and artery revascularization procedures, myocardial infarction, and unstable symptomatic ischemic heart disease.Xx_NEWLINE_xXIschemic cerebrovascular event, including transient ischemic attack and artery, revascularization procedures.Xx_NEWLINE_xXCerebrovascular disease manifested as prior stroke at any time or transient ischemic attack (TIA) in the 12 months prior to initiation of therapyXx_NEWLINE_xXAbsence of the following in the previous 6 months:\r\n* Myocardial infarction;\r\n* Unstable angina pectoris;\r\n* Clinically-significant cardiac arrhythmias;\r\n* Stroke (including transient ischemic attack [TIA], or other ischemic event);\r\n* Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [eg, vena cava filter] are not eligible for this study)Xx_NEWLINE_xXCerebral vascular accident (CVA) or transitory ischemic attack (TIA) in the year before enrollment, or presence of residual symptoms from CVA that happened more than a year beforeXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXAngina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatmentXx_NEWLINE_xXHistory of hemorrhagic or ischemic stroke within the last 6 monthsXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to ongoing or active infection; any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolismXx_NEWLINE_xXAny history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to registration.Xx_NEWLINE_xXAny of the following within 6 months before the first dose of study treatment:\r\n* Unstable angina pectoris\r\n* Clinically-significant cardiac arrhythmias\r\n* Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n* Myocardial infarction\r\n* Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)Xx_NEWLINE_xXIschemic myocardial event, including angina requiring therapy and artery revascularization procedures.Xx_NEWLINE_xXIschemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to registrationXx_NEWLINE_xXHistory of any of the following within the last 6 months prior to study entry: ischemic myocardial event, including angina requiring therapy and artery revascularization procedures; ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures; requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); placement of a pacemaker for control of rhythm; New York Heart Association (NYHA) class III or IV heart failure; pulmonary embolismXx_NEWLINE_xXHistory of prior cerebrovascular event, (including transient ischemic attack) within 6 months of start of screeningXx_NEWLINE_xXAny of the following conditions =< 6 months prior to registration:\r\n* Cerebrovascular accident (CVA) or transient ischemic attack (TIA)\r\n* Serious or unstable cardiac arrhythmia\r\n* Admission for unstable angina or myocardial infarction\r\n* Cardiac angioplasty or stenting\r\n* Coronary artery bypass graft surgery\r\n* Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation =< 30 days\r\n* Arterial thrombosis\r\n* Symptomatic peripheral vascular diseaseXx_NEWLINE_xXAny history of cerebrovascular accident or transient ischemic attackXx_NEWLINE_xXHistory of any of the following within the last 6 months before administration of the first dose of the drug:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolismXx_NEWLINE_xXArterial thromboembolic event including, but not limited to, myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months of enrollmentXx_NEWLINE_xXHistory of any of the following:\r\n* Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)\r\n* Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial within 6 months prior to randomization\r\n* Venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks) within 6 months prior to randomization\r\n* Clinically significant ventricular arrhythmias within 6 months prior to randomizationXx_NEWLINE_xXWithin the past 6 months, has had any of the following: pleural effusion, myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attackXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXSignificant arterial or venous thromboembolic disease or vascular disorders within 6 months prior to administration of first dose of study drug, including by not limited to:\r\n* Cerebrovascular accident (CVA) or transient ischemic attack (TIA)\r\n* Peripheral ischemia > grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version 4.0)\r\n* Arterial thrombotic eventXx_NEWLINE_xXWithin the past 6 months, has had any of the following: myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attackXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXPHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: History of stroke, transient ischemic attack (TIA), or myocardial infarction, within 6 months prior to C1D1Xx_NEWLINE_xXAny of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attackXx_NEWLINE_xXAny of the following within 6 months of registration: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism; no QTc interval > 480 msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or torsade de pointesXx_NEWLINE_xXThe patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollmentXx_NEWLINE_xXHistory of any of the following within the last 6 months prior to study entry: ischemic myocardial event, including angina requiring therapy and artery revascularization procedures; ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures; requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); placement of a pacemaker for control of rhythm; New York Heart Association (NYHA) class III or IV heart failure; pulmonary embolismXx_NEWLINE_xXHistory of any of the following:\r\n* Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)\r\n* Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization\r\n* Any condition that in the opinion of the investigator, would preclude participation in this studyXx_NEWLINE_xXHistory of any of the following within the last 6 months before administration of the\r\nfirst dose of the drug:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolismXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 3 months prior to cycle 1, day 1Xx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of any of the following within the last 6 months prior to study entry:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolismXx_NEWLINE_xXAny of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolismXx_NEWLINE_xXCAPMATINIB EXCLUSION CRITERIA: Any of the following in the past 6 months prior to screening:\r\n* Myocardial infarction\r\n* Severe/unstable angina\r\n* Clinically significant cardiac arrhythmias\r\n* Cerebrovascular accident or transient ischemic attack\r\n* Coronary/peripheral artery bypass graftXx_NEWLINE_xXCERITINIB EXCLUSION CRITERIA: Any of the following in the past 6 months prior to screening:\r\n* Myocardial infarction\r\n* Severe/unstable angina\r\n* Clinically significant cardiac arrhythmias\r\n* Cerebrovascular accident or transient ischemic attack\r\n* Coronary/peripheral artery bypass graftXx_NEWLINE_xXREGORAFENIB EXCLUSION CRITERIA: Any of the following in the past 6 months prior to screening:\r\n* Myocardial infarction\r\n* Severe/unstable angina\r\n* Clinically significant cardiac arrhythmias\r\n* Cerebrovascular accident or transient ischemic attack\r\n* Coronary/peripheral artery bypass graftXx_NEWLINE_xXENTRECTINIB EXCLUSION CRITERIA: Any of the following in the past 6 months prior to screening:\r\n* Myocardial infarction\r\n* Severe/unstable angina\r\n* Clinically significant cardiac arrhythmias\r\n* Cerebrovascular accident or transient ischemic attack\r\n* Coronary/peripheral artery bypass graftXx_NEWLINE_xXHistory or presence of serious hemorrhage , hemoptysis or hematemesis within 3 months or a thromboembolic event (including Deep Vein Thrombosis (DVT), stroke and/or transient ischemic attack) within 6 months; Patients with squamous Non Small Cell Lung Cancer (NSCLC) should be excluded.Xx_NEWLINE_xXCerebrovascular event (transient ischemic attack, stroke or CNS bleeding) within the last 12 months.Xx_NEWLINE_xXThe patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollmentXx_NEWLINE_xXAny of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE grade >= 2, symptomatic congestive heart failure, or cerebrovascular accident excluding transient ischemic attackXx_NEWLINE_xXHistory of any of the following:\r\n* Seizure or known condition that may predispose to seizure (e.g., prior stroke within 1 year of randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)\r\n* Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomizationXx_NEWLINE_xXAny of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular accident, transient ischemic attackXx_NEWLINE_xXAny history of myocardial infarction (MI), unstable angina, cerebrovascular accident, or Transient Ischemic Attack (TIA)Xx_NEWLINE_xXPHASE I STUDY ELIGIBILITY CRITERIA:\r\nHistory of cerebrovascular accident, transient ischemic attack within 1 year prior to study enrollmentXx_NEWLINE_xXPHASE II STUDY COHORT 5 TRIPLE NEGATIVE BREAST CANCER ELIGIBILITY CRITERIA (MEDI+O ONLY):\r\nHistory of cerebrovascular accident, transient ischemic attack within 1 year prior to study enrollmentXx_NEWLINE_xXPHASE II COLORECTAL CANCER COHORT 6 (MEDI+C ONLY):\r\nHistory of cerebrovascular accident, transient ischemic attack within 1 year prior to study enrollmentXx_NEWLINE_xXCerebrovascular accident or transient ischemic attackXx_NEWLINE_xXHistory of stroke or transient ischemic attack within six monthsXx_NEWLINE_xXloss of consciousness or transient ischemic attack within 12 months of randomizationXx_NEWLINE_xXAngina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery (CABG) within the past 6 months; deep venous thrombosis within 6 months, unless the patient is anticoagulated without the use of warfarin for at least 2 weeks; in this situation, low molecular weight heparin is preferredXx_NEWLINE_xXPatients with stroke or transient ischemic attack (TIA) within 90 days prior to enrollment; or peripheral vascular disease requiring intervention within the 90 days prior to enrollment; or any known hemodynamically significant lesion or embolic plaqueXx_NEWLINE_xXPatients with any history of arterial thromboembolic disease; any patient with a history of myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina or peripheral vascular disease will not be eligibleXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to study enrollmentXx_NEWLINE_xXHistory of any of the following within the last 6 months prior to study entry:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* Pulmonary embolismXx_NEWLINE_xXHistory of any cardiac events including coronary revascularization or ischemic symptomsXx_NEWLINE_xXAngina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to day 1Xx_NEWLINE_xXHistory of any cardiac events including coronary revascularization or ischemic symptomsXx_NEWLINE_xXSevere cardiovascular disease within 6 months, including myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebro-vascular accident or transient ischemic attack, pulmonary embolism, life threatening arrhythmias, uncontrollable hypertension or QT prolongation syndromeXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXPatients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* History or presence of serious uncontrolled ventricular or significant arrhythmias\r\n* Any of the following within 6 months prior to registration: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE)\r\n* Uncontrolled hypertension (defined by a systolic blood pressure [SBP] >= 160 mmHg or diastolic blood pressure [DBP] >= 100 mmHg while on anti-hypertensive medications) or history of hypertensive crisis or hypertensive encephalopathy, stroke, TIA, symptomatic peripheral vascular disease, or grade 2 CHFXx_NEWLINE_xXHistory of biliary colic attackXx_NEWLINE_xXPatients with history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment on this studyXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizures at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months of screeningXx_NEWLINE_xXCerebrovascular accident or transient ischemic attack within 6 months prior to first dose.Xx_NEWLINE_xXExperience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, =< 6 months prior to randomizationXx_NEWLINE_xXPatients with symptomatic congestive heart failure, unstable angina or myocardial infarction, coronary/peripheral artery bypass graft or repair, cerebrovascular accident or transient ischemic attack in the 12 months prior to randomization; or deep vein thrombosis or pulmonary embolism in the 6 months prior to randomizationXx_NEWLINE_xXHistory of clinically significant vascular disease, including any of the following within 6 months prior to day 1 of study drug: myocardial infarction or unstable angina, percutaneous coronary intervention, bypass grafting, ventricular arrhythmia requiring medication, stroke or transient ischemic attack, symptomatic peripheral arterial disease and/or involvement of great vessels by tumor with or without vascular graftingXx_NEWLINE_xXHistory of transient ischemic attack (TIA) or stroke within 6 months of study entryXx_NEWLINE_xXStroke within 6 months of screening, or transient ischaemic attack (TIA) within 3 months of screeningXx_NEWLINE_xXHistory of cerebrovascular accident including transient ischemic attack (TIA), myocardial infarction, pulmonary embolism or untreated deep venous thrombosis (DVT), coronary artery bypass graft surgery within 6 months prior to registration; Note: subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligibleXx_NEWLINE_xX215 History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of AMG 562.Xx_NEWLINE_xXHistory of transient ischemic attack within the previous 6 monthsXx_NEWLINE_xXHistory of loss of consciousness or transient ischemic attack within twelve (12) months of enrollmentXx_NEWLINE_xXAny of the following: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE grade >= 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, uncontrolled seizures or brain metastases or pulmonary embolism.Xx_NEWLINE_xXHistory of active coronary or ischemic symptomsXx_NEWLINE_xXHistory of an ischemic insult in the previous 12 months (myocardial infarction, cerebral vascular accident, ischemic tissue from injury, transient ischemic attack)Xx_NEWLINE_xXHistory of seizures except for remote with specific etiology which has resolved (ex: alcohol induced seizure); transient ischemic attack (TIA) or cerebrovascular accident (CVA) within last 6 monthsXx_NEWLINE_xXPatient has a history of seizures or any condition that may predispose to seizures (e.g., prior cortical stroke, significant brain trauma) at any time in the past and/or a history of loss of consciousness or transient ischemic attack within 12 months of the cycle 1, day 1 visit.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack =< 6 months prior to registrationXx_NEWLINE_xXHistory of loss of consciousness or transient ischemic attack within 12 months prior to enrollmentXx_NEWLINE_xXHistory of transient ischemic attack (TIA) or cerebrovascular accident (CVA)Xx_NEWLINE_xXPatients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures which are not controlled with non-enzyme inducing anticonvulsants, any brain metastases and/or epidural disease, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior to the first date of study treatmentXx_NEWLINE_xXHistory of stroke or transient ischemic attack within six monthsXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to Day1Xx_NEWLINE_xXThe subject has uncontrolled or significant intercurrent illness including, but not limited to,\r\nthe following conditions:\r\n* Cardiovascular disorders such as symptomatic congestive heart failure (CHF), uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening), unstable angina pectoris, clinically-significant cardiac arrhythmias, history of stroke (including transient ischemic attack [TIA], or other ischemic event) within 6 months of study treatment, myocardial infarction within 6 months of study treatment, history of thromboembolic event requiring therapeutic anticoagulation within 6 months of study treatment or main portal vein or vena cava thrombosis or occlusion; (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)Xx_NEWLINE_xXPatients with a history of seizures, predisposing factors for seizures, including underlying brain injury with loss of consciousness within previous 12 months, transient ischemic attack within previous 12 months, cerebral vascular accident or brain arteriovenous malformationXx_NEWLINE_xXArterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or MI within 6 months of study registrationXx_NEWLINE_xXIschemic myocardial event including angina requiring therapy and artery revascularization proceduresXx_NEWLINE_xXIschemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization proceduresXx_NEWLINE_xXAny history of seizure; history of loss of consciousness or transient ischemic attack within 12 months of starting the study drugXx_NEWLINE_xXAny of the following within 6 months prior to first dose of treatment: myocardial infarction, symptomatic coronary artery disease (severe or unstable angina), artery bypass graft, uncontrolled arrhythmias, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolusXx_NEWLINE_xXPatients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligibleXx_NEWLINE_xXPatients with history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study are ineligibleXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to study enrollmentXx_NEWLINE_xXHistory or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months of Cycle 1 DayXx_NEWLINE_xXPrior history of cerebrovascular accident or transient ischemic attack.Xx_NEWLINE_xXSubject with a history of loss of consciousness or transient ischemic attack ? 12 months of study drug initiation.Xx_NEWLINE_xXNo history of acute arterial thrombotic events within the past 6 months (including cerebrovascular accident [CVA], transient ischemic attack [TIA], myocardial infarction [MI], or unstable angina)Xx_NEWLINE_xXPatient must have no history of cerebrovascular accident (CVA) within 6 months of randomizationXx_NEWLINE_xXHave experienced any arterial or venothrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, within 6 months (?6 months) prior to randomization.Xx_NEWLINE_xXAny of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolismXx_NEWLINE_xXAny of the following within 6 months of randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 Grade ?2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.Xx_NEWLINE_xXNo clinically significant cardiovascular disease\r\n* Patients with a history of hypertension must be well controlled (< 150/90) on a regimen of antihypertensive therapy\r\n* History of arterial thrombotic events within the past 6 months, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina, or angina requiring surgical or medial intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection) are not eligible\r\n* Patients who have had a deep vein thrombosis or pulmonary embolus within the past 6 months are eligible if they are on stable therapeutic anticoagulation\r\n* No current New York Heart Association classification II, III, or IV congestive heart failureXx_NEWLINE_xXHistory of stroke or transient ischemic attacks within 6 months prior to study enrolment.Xx_NEWLINE_xXCerebrovascular accident or transient ischemic attackXx_NEWLINE_xXSubject has history of loss of consciousness or transient ischemic attack within 12 months prior to day 1.Xx_NEWLINE_xXAny of the following within 12 months prior to enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of Grade greater than or equal to (>/=) 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, or cerebrovascular accident including transient ischemic attackXx_NEWLINE_xXPatients must have international normalized ratio (INR) =< 1.2 within 14 days prior to registration; patients must not be receiving warfarin for therapeutic use, have history of cerebrovascular accident (CVA), history of transient ischemic attack (TIA) requiring intervention or treatment, pre-existing carotid artery disease requiring intervention or treatment, or current use of megestrol acetate (use within 10 days of registration)Xx_NEWLINE_xXPatients are excluded if they have a history of stroke or transient ischemic attack within 6 months prior to randomizationXx_NEWLINE_xXPatients with active vascular disease, either myocardial or peripheral (i.e. acute coronary syndrome, cerebral stroke, transient ischemic attack or arterial thrombosis or symptomatic peripheral vascular disease within the past 3 months);Xx_NEWLINE_xXRecent (=< 6 months) arterial thromboembolic events, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarctionXx_NEWLINE_xXPatients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first dose of study drug.Xx_NEWLINE_xXHistory of ischemic cardiac disease that has occurred within 6 months prior to study entry.Xx_NEWLINE_xXThe subject has a history of loss of consciousness, cerebrovascular accident, or transient ischemic attack within 12 months before the Day 1 visit.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to cycle 1, day 1Xx_NEWLINE_xXHistory or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident (CVA)/stroke or transient ischemic attack (TIA) or sub-arachnoid hemorrhage within =< 6 months prior to the first study treatmentXx_NEWLINE_xXIschemic myocardial event, including angina requiring therapy and artery revascularization procedures;Xx_NEWLINE_xXIschemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures;Xx_NEWLINE_xXWithin 6 months prior to randomization, have had any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack.Xx_NEWLINE_xXHistory or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures which are not controlled with non-enzyme inducing anticonvulsants, any brain metastases and/or epidural disease, or history of cerebrovascular accident (cerebrovascular accident [CVA], stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior to the first date of study treatmentXx_NEWLINE_xXHistory of stroke, deep venous thrombosis (DVT), or transient ischemic attack (TIA)Xx_NEWLINE_xXHave experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.Xx_NEWLINE_xXHistory of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registrationXx_NEWLINE_xXCerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months prior to the first date of study therapy.Xx_NEWLINE_xXPrevious history of cerebrovascular accident (CVA), transient ischemic attack (TIA), angina pectoris, acute myocardial infarction (MI) or history of recent re-perfusion procedures (e.g. percutaneous transluminal coronary angioplasty [PTCA]), pulmonary embolus or untreated deep vein thrombosis (DVT) within 6 months from day 1 of study drug; NOTE: subjects with recent DVT who have been therapeutically anti-coagulated for at least 6 weeks are eligibleXx_NEWLINE_xXHistory of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 monthsXx_NEWLINE_xXAny of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attackXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 monthsXx_NEWLINE_xXKnown active brain or central nervous system metastasis (less than 1 month out from definitive radiotherapy or surgery), or seizures requiring anticonvulsant treatment, or clinically significant cerebrovascular accident or transient ischemic attack (< 3 months)Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to beginning treatment.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack, or other arterial thrombosis =< 12 months prior to randomizationXx_NEWLINE_xXStroke, transient ischemic attack, arterial embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within the past 6 monthsXx_NEWLINE_xXHistory (within the previous year) of stroke or transient ischemic attack, unstable angina, myocardial infarction, hospitalization for acutely decompensated congestive heart failureXx_NEWLINE_xXAny of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attackXx_NEWLINE_xXSubject has a history of loss of consciousness or transient ischemic attack within 12 months before the Day 1 visit.Xx_NEWLINE_xXHistory of any of the following within the last 6 months prior to study entry:\r\n*Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure \r\n* Pulmonary embolismXx_NEWLINE_xXAny of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism.Xx_NEWLINE_xXPrior history of cerebrovascular accident or transient ischemic attack, or pre-existing carotid artery diseaseXx_NEWLINE_xXPatients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.Xx_NEWLINE_xXHas a history of an arterial thromboembolic event within the prior six months including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina.Xx_NEWLINE_xXloss of consciousness or transient ischemic attack within 12 months of randomizationXx_NEWLINE_xXThe participant experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.Xx_NEWLINE_xXSubjects with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or, within six months prior to Day 1 of this study, history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage.Xx_NEWLINE_xXParticipants may not have had a history of a stroke or transient ischemic attack within six monthsXx_NEWLINE_xXHas had clinically significant cardiovascular disease within 12 months of start of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stentXx_NEWLINE_xXPatients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment on this studyXx_NEWLINE_xXArterial thrombotic events =< 6 months prior to randomization; Note: this includes transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI)Xx_NEWLINE_xXHistory of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 monthsXx_NEWLINE_xXPatients must have not have a history of hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding 6 months that were not related to glioma surgeryXx_NEWLINE_xXPatients with a cerebrovascular accident or transient ischemic attack within the past six monthsXx_NEWLINE_xXPatients with any of the following conditions are excluded:\r\n* Serious or non-healing wound, ulcer, or bone fracture\r\n* History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 28 days of treatment\r\n* Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry\r\n* History of myocardial infarction, ventricular arrhythmia, stable/unstable angina, symptomatic congestive heart failure, coronary/peripheral artery bypass graft or stenting or other significant cardiac disease within 12 months prior to study entry\r\n* Any history of arterial or venous thrombosis/thromboembolic event, including pulmonary embolism within the past 12 months\r\n* Any episode of atrial fibrillation in the prior 12 monthsXx_NEWLINE_xXHistory of cerebrovascular attack or transient ischemic attack within 6 months prior to the initiation of therapy on this protocolXx_NEWLINE_xXIn past 12 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attackXx_NEWLINE_xXStroke or transient ischemic attackXx_NEWLINE_xXPatients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this studyXx_NEWLINE_xXCerebrovascular accident or transient ischemic attack within 6 months prior to first doseXx_NEWLINE_xXAny of the following within the preceding 6 months- myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass, graft, cerebrovascular accident or transient ischemic attack, clinically significant bleedingXx_NEWLINE_xXMyocardial infarction and transient ischemic attack or stroke within 6 months prior to enrollmentXx_NEWLINE_xXHistory of loss of consciousness or transient ischemic attack within 12 months prior to enrollmentXx_NEWLINE_xXhistory of cerebrovascular accident (CVA) or transient ischemic attack (TIA),Xx_NEWLINE_xXAny of the following within 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and within 6 months before study drug administration for deep vein thrombosis or pulmonary embolismXx_NEWLINE_xXNo arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, myocardial infarction (MI), or unstable angina or angina requiring surgical or medical intervention in 6 months prior to registration; patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible; patients who have experienced a deep venous thrombosis or pulmonary embolus within 6 months prior to registration must be on stable therapeutic anticoagulation for at least 6 weeks prior to enrollment of this studyXx_NEWLINE_xXPrior history of cerebrovascular accident or transient ischemic attackXx_NEWLINE_xXHistory of a stroke or transient ischemic attack within 6 monthsXx_NEWLINE_xXPatients who have had a myocardial infarction, transient ischemic attack, unstable angina, or cardiovascular symptoms (CVS) within 6 months before treatmentXx_NEWLINE_xXHistory of aortic aneurysm, aortic dissection, angina, myocardial infarction, stroke, transient ischemic attack, or other arterial thrombotic events within 6 months of registration; patients on therapeutic non-coumarin anticoagulation are eligible provided that they are on a stable dose of anticoagulantsXx_NEWLINE_xX-  History of stroke or transient ischemic attack within 6 months prior to Day 1.Xx_NEWLINE_xXHistory of significant cerebrovascular disease (i.e. stroke or transient ischemic attack [TIA]) in the past 6 months or ongoing event with active symptoms or sequelaeXx_NEWLINE_xXClinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stentXx_NEWLINE_xXHistory of an arterial thrombotic vascular event including cerebrovascular accident (CVA), myocardial infarction (MI), unstable angina, coronary or peripheral arterial bypass graft, or transient ischemic attack (TIA) within 6 monthsXx_NEWLINE_xXHistory or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident (CVA)/stroke or transient ischemic attack (TIA) or sub-arachnoid hemorrhage within =< 6 months prior to the first study treatmentXx_NEWLINE_xXSymptomatic coronary artery disease, cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina pectoris within 6 months of screeningXx_NEWLINE_xXAny of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attackXx_NEWLINE_xXHistory of cerebrovascular accident, including transient ischemic attack (TIA)Xx_NEWLINE_xXAny of the following within 6 months prior to trial registration: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic eventXx_NEWLINE_xXHistory of cerebral vascular accident (CVA) or transient ischemic attack (TIA) =< 6 months prior to randomizationXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to day 1Xx_NEWLINE_xXHistory of arterial thrombotic events within 6 months before randomization, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (e.g., claudication with < 1 block) or any other arterial thrombotic event are also ineligibleXx_NEWLINE_xXClinical significant uncontrolled conditions â€\ active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.Xx_NEWLINE_xXPrior history of stroke or transient ischemic attack within 6 months prior to day -3Xx_NEWLINE_xXHistory of cerebrovascular accident including transient ischemic attack within the past 12 monthsXx_NEWLINE_xXHistory of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 months prior to day 1Xx_NEWLINE_xXFor Arm D only: History of seizure, unexplained loss of consciousness, transient ischemic attack within 12 months of enrollment, cerebral vascular accident, and any brain metastasesXx_NEWLINE_xXPatients with a history of myocardial infarction, unstable angina, stroke, or transient ischemic attack (TIA) within 6 months prior to planned day 1 of dosing are ineligibleXx_NEWLINE_xXAny of the following in the past 6 months: myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosisXx_NEWLINE_xXUncontrolled intercurrent illness including infection, congestive heart failure, myocardial infarction, transient ischemic attack or stroke within 6 months; any such conditions that have occurred in the last 6 months but are no longer active at the time of registration are not considered exclusionaryXx_NEWLINE_xXPatients with a history of embolic events (e.g. transient ischemic attack [TIA]) from arrhythmia or peripheral arterial disease or of recent myocardial infarction (MI) whether or not treated with anti-platelet drugsXx_NEWLINE_xXPatients with cerebrovascular accident or transient ischemic attack within 6 months of therapy are excludedXx_NEWLINE_xXHistory of stroke or transient ischemic attackXx_NEWLINE_xXHistory of stroke or transient ischemic attack within six monthsXx_NEWLINE_xXPatients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.Xx_NEWLINE_xXPatients known or suspected to have hypercoagulable syndrome or with history of venous or arterial thrombosis, stroke, transient ischemic attack (TIA), or pulmonary embolismXx_NEWLINE_xXAny of the following in the past 6 months: myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosisXx_NEWLINE_xXHistory of a stroke or cerebrovascular accident (CVA) within 6 monthsXx_NEWLINE_xXUncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy) or any of the following within 12 months prior to registration: myocardial infarction, congenital long QT syndrome, torsade de points, arrhythmias, right bundle branch block and left anterior hemiblock uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, ongoing NCICTCAE Grade 2 cardiac dysrhythmias, atrial fibrillation or QTcF interval >470 msec.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack (TIA) within 6 months prior to Cycle 1, Day 1Xx_NEWLINE_xXHistory of loss of consciousness or transient ischemic attack within 12 months of enrollmentXx_NEWLINE_xXHistory of seizure or any condition that may predispose to seizures (e.g., prior cortical stroke or significant brain trauma) at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months of screening.Xx_NEWLINE_xXAny of the following within 6 months prior to study entry:\r\n* Myocardial infarction (MI)\r\n* Severe/unstable angina\r\n* Coronary artery bypass graft (CABG)\r\n* Congestive heart failure (CHF) > New York Heart Association (NYHA) II\r\n* Cerebrovascular accident (CVA)\r\n* Transient ischemic attack (TIA)\r\n* Pulmonary embolism (PE)Xx_NEWLINE_xXHistory of cerebrovascular accident or transient ischemic attack.Xx_NEWLINE_xXCerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 12 weeks prior to Baseline.Xx_NEWLINE_xXUncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months before enrollment, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication.Xx_NEWLINE_xXUncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months before enrollment, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication.Xx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to Day 1Xx_NEWLINE_xXAny of the following within the 6 months prior to study drug administration: myocardial infarction, grade 2 or greater peripheral vascular disease, arterial thrombotic event, visceral arterial ischemia, cerebrovascular ischemia, transient ischemic attack, percutaneous transluminal angioplasty or stent, or unstable anginaXx_NEWLINE_xXSignificant or active cardiovascular disease, specifically including but not restricted to:\r\n* History of myocardial infarction \r\n* History of atrial or ventricular arrhythmia\r\n* Unstable angina within 6 months prior to first dose of ponatinib\r\n* History of congestive heart failure \r\n* Left ventricular ejection fraction (LVEF) less than lower limit of normal \r\n* History of peripheral arterial occlusive disease \r\n* History of cerebrovascular accident or transient ischemic attack \r\n* Venous thromboembolism including deep venous thrombosis or pulmonary embolism within 6 months prior to enrollmentXx_NEWLINE_xXMyocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor.Xx_NEWLINE_xXAny history of major myocardial infarction, stroke or transient ischemic attack (TIA); minor acute myocardial infarction (AMI) and patients who have had cardiac bypass free of symptoms for at least 2 years may be eligible at the discretion of the study chairXx_NEWLINE_xXHistory of cerebrovascular accident (CVA) within 6 months prior to registration or that is not stable.Xx_NEWLINE_xXSUNITINIB MALATE ARM: Patients with any of the following conditions are excluded:\r\n* Serious or non-healing wound, ulcer, or bone fracture\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment\r\n* Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry\r\n* History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry\r\n* History of pulmonary embolism within the past 12 monthsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXParticipants with a recent history (< 6 months) of a major infarct including but not inclusive to bowel ischemia, cerebral vascular accident, transient ischemic attack, myocardial infarction, limb ischemia, or skin necrosisXx_NEWLINE_xXPast history of stroke or transient ischemic attack requiring medical therapyXx_NEWLINE_xXHistory of an ischemic insult in the previous 12 months (myocardial infarction, cerebral vascular accident, ischemic tissue from injury, transient ischemic attack.Xx_NEWLINE_xXParticipant has experienced any arterial thromboembolic event (ATE), including myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, within 6 months prior to receiving study drugs.Xx_NEWLINE_xXThe subject has the following cardiac conditions: unstable angina pectoris, clinically significant cardiac arrhythmias, history of stroke (including transient ischemic attack [TIA], or other ischemic event) within 6 months of study treatment, myocardial infarction within 6 months of study treatment, history of thromboembolic event requiring therapeutic anticoagulation within 6 months of study treatment or main portal vein or vena cava thrombosis or occlusion; (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)Xx_NEWLINE_xXHistory of hemorrhagic or ischemic stroke within 6 months prior to first dose of mirvetuximab soravtansineXx_NEWLINE_xXHistory of a stroke or transient ischemic attack, unstable angina, myocardial infarction, or cardiac symptoms within 6 months prior to the first dose of treatment.Xx_NEWLINE_xXConcomitant diseases/conditions: Unstable angina, myocardial infarction, valvular heart disease, encephalopathy, ischemic attacks, hemorrhagic or ischemic cerebrovascular accident (CVA) or ongoing pulmonary embolism within last year, arrhythmia, hepatopathy, uncontrolled infection, hemoptysis or oxygen requiring dyspnea, known HIV infection, bleeding risk, muscular problems, peripheral neuropathy, Symptomatic or progressive brain metastases or leptomeningeal disease.Xx_NEWLINE_xXAny of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically significant bleeding or pulmonary embolismXx_NEWLINE_xXHistory of cerebrovascular attack or transient ischemic attack within 6 months prior to the initiation of therapy on this protocol.Xx_NEWLINE_xXAny of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event, or pulmonary embolismXx_NEWLINE_xXSymptomatic peripheral vascular disease, stroke or transient ischemic attack within 6 monthsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXAny of the following within the 12 months prior to registration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.Xx_NEWLINE_xXHistory of prior cerebrovascular accident (CVA), including transient ischemic attach (TIA)Xx_NEWLINE_xXCardiomyopathy or history of ischemic heart disease. o Participants with ischemic heart disease who have had acute coronary syndrome (ACS), myocardial infarction (MI), or revascularization (example, coronary artery bypass graft, stent) in the past 6 months are excluded. However, participants with ischemic heart disease who have had ACS, MI, or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll.Xx_NEWLINE_xXPatients with either of the following within 6 months before the first dose of study treatment:\r\n* Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n* Myocardial infarctionXx_NEWLINE_xXHave experienced any of the following within the 6-month period prior to screening: angina pectoris, coronary artery disease or cerebrovascular accident, transient ischemic attack, cardiac failure with known ejection fraction less than 40%, or cardiac arrhythmia requiring medical therapyXx_NEWLINE_xXAny of the following within 3 months prior to study drug administration: myocardial infarction, unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolismXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 3 months prior to registrationXx_NEWLINE_xXPatient is at increased bleeding risk due to concurrent conditions (eg, major injuries or surgery within the past 28 days prior to start of study treatment, history of CVA, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).Xx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXCerebrovascular accident or transient ischemic attack within 2 yearsXx_NEWLINE_xXClinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stentXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to beginning treatment.Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to study enrollmentXx_NEWLINE_xXHas experienced any arterial thrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months prior to randomizationXx_NEWLINE_xXHistory of any of the following within the last 6 months before administration of the first dose of the drug:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures,\r\n* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures,\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia),\r\n* Placement of a pacemaker for control of rhythm,\r\n* New York Heart Association (NYHA) class III or IV heart failure, -Pulmonary embolismXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of coronary revascularization or ischemic symptomsXx_NEWLINE_xXHistory of cerebrovascular accident within the past 6 months (e.g. transient ischemic attack [TIA])Xx_NEWLINE_xXHistory of stroke or transient ischemic attack within 6 months prior to day 1Xx_NEWLINE_xXNo history of arterial thrombotic events within the past 6 months, including:\r\n* Transient ischemic attack (TIA)\r\n* Cerebrovascular accident (CVA)\r\n* Peripheral arterial thrombus\r\n* Unstable angina or angina requiring surgical or medial intervention\r\n* Myocardial infarction (MI)\r\n* Significant peripheral artery disease (i.e., claudication on less than one block)\r\n* Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection)Xx_NEWLINE_xXHistory of dementia, Alzheimer’s disease, multi-infarct dementia or cerebrovascular accident (CVA) (history of transient ischemic attack [TIA] is allowed)Xx_NEWLINE_xXHave experienced any of the following within the 6-month period prior to screening: angina pectoris, coronary artery disease or cerebrovascular accident, transient ischemic attack, cardiac failure with known ejection fraction less than 40%, or severe uncontrolled ventricular arrhythmia.Xx_NEWLINE_xXCerebrovascular accident (CVA), transient ischemic attack (TIA) within the last 6 months prior to registrationXx_NEWLINE_xXHistory of stroke or transient ischemic attack within 3 months of first study doseXx_NEWLINE_xXAny contraindications to vigorous exercise, including, but not limited to: brain metastases; current congestive heart failure (New York Heart Association class II, III or IV); serious or non-healing wound, ulcer, or bone fracture; spinal cord compromise or instrumentation due to metastatic disease; peripheral neuropathy >= grade 3; no serious cardiovascular events within 12 months including, but not limited to, transient ischemic attack (TIA), cerebrovascular accident (CVA), or myocardial infarction (MI)Xx_NEWLINE_xXCerebrovascular accident (CVA) or stroke within the past 6 monthsXx_NEWLINE_xXSubjects with history of evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within six months of study entryXx_NEWLINE_xXPatients must not have recent (within six months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or class III/IV heart failureXx_NEWLINE_xXNo history of stroke or transient ischemic attackXx_NEWLINE_xXHistory of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to Day 1Xx_NEWLINE_xXAny arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, <6 months prior to randomization.Xx_NEWLINE_xXHistory of cardiovascular disease including prior myocardial infarction, angina, stroke, or transient ischemic attack (TIA)Xx_NEWLINE_xXAtherosclerotic cardiovascular disease (ASCVD) defined by history of acute coronary syndromes, myocardial infarction (MI), stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral arterial disease presumed to be of atherosclerotic originXx_NEWLINE_xXClinical history of cardiovascular disease (CVD) occurring within the past 6 months, including myocardial infarction, angina, coronary revascularization, stroke, transient ischemic attack (TIA), carotid revascularization, peripheral arterial disease, and congestive heart failureXx_NEWLINE_xXPatients with a history of any of the following within the last 6 months prior to study entry are ineligible:\r\n* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n* Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures\r\n* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n* Placement of a pacemaker for control of rhythm\r\n* New York Heart Association (NYHA) class III or IV heart failure\r\n* Pulmonary embolismXx_NEWLINE_xXSubject has coronary artery disease with an ischemic event within 6 months prior to enrollment.Xx_NEWLINE_xXHistory of cerebrovascular accident or transient ischemic attack within 3 months of first study doseXx_NEWLINE_xXheart attack, acute (2 days) cardiac event or stroke in preceding six months,Xx_NEWLINE_xXPatient must not have a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure =< 6 months prior to study entryXx_NEWLINE_xXHistory of progressive promyelocytic leukemia (PML), known history of pancreatitis, active grade 3 or higher viral, bacterial or fungal infection =< 2 weeks prior to registration and documented history of cerebrovascular event (stroke or transient ischemic attack [TIA]) =< 6 months prior to registrationXx_NEWLINE_xXStroke or transient ischemic attack within 6 months of screeningXx_NEWLINE_xXUncontrolled active seizure disorder or history of cerebrovascular accident (CVA) or transient ischemic (TI) attack within the past 12 monthsXx_NEWLINE_xXSubjects with a history of evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within six months of study entryXx_NEWLINE_xXHistory of stroke or transient ischemic attack in the preceding 6 monthsXx_NEWLINE_xXHistory of stroke/transient ischemic attackXx_NEWLINE_xXHistory of loss of consciousness or transient ischemic attack within past 12 monthsXx_NEWLINE_xXAny of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, or cerebrovascular accident including transient ischemic attack.Xx_NEWLINE_xXOccurrence of heart attack, stroke, or angina in the past 3 monthsXx_NEWLINE_xXUnstable angina, myocardial infarction, known or suspected transient ischemic events, or stroke within 24 weeks of start of Screening.Xx_NEWLINE_xXAngina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within the past 6 months. Deep venous thrombosis within 6 months, unless the patient is therapeutically anti-coagulated for at least 2 weeks. In this situation, low molecular weight heparin is preferredXx_NEWLINE_xX