​​Master Protocol of Novel Study Interventions and Combinations in Participants with Colorectal Cancer​

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• ​​Master: 1 Central nervous system metastases or spinal cord compression (including asymptomatic and adequately treated disease, unless specified in the respective substudy protocol). Participants with suspected brain metastases at screening should have an MRI (preferred) or CT scan, each preferably with IV contrast of the brain prior to randomization​
• ​​Sub 1: 2 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including, but not limited to, ongoing or active infection, ILD, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations, and active bleeding diseases) and/or history of organ transplant or allogenic stem cell transplant, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol
• ​​Sub 1: 3 Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (eg, colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, sarcoidosis syndrome, Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, pneumonitis (past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD) etc​.
• ​​Sub 1: 4 Any of the following cardiac conditions : ​− Cardiomyopathy of any etiology or history of myocarditis ​− Heart failure (as defined by New York Heart Association class III-IV) ​− Uncontrolled hypertension defined as diastolic blood pressure ≥ 90 mmHg or systolic blood pressure ≥ 140 mmHg ​− Unstable angina pectoris ​− Clinically significant coronary, carotid, or peripheral artery stenosis ​− Acute coronary syndrome/acute myocardial infarction and/or coronary intervention with percutaneous coronary intervention/coronary artery bypass grafting within 12 months prior to randomization ​− Prior arterial or peripheral vascular intervention within 12 months prior to ​randomization ​− Ventricular arrhythmias requiring treatment, high degree AV block (II-III), or sinus node dysfunction with significant sinus pause, untreated with pacemaker. Note: Patients with atrial fibrillation or flutter who are clinically stable and have an optimally controlled ventricular rate (eg, mean of < 100 bpm on resting ECG or 24-hour Holter-ECG) may be eligible if all other cardiac eligibility criteria are met, and a cardiology assessment confirms suitability for study treatment. ​− History of QT prolongation associated with other medications that required discontinuation of that medication. ​− Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives. ​− Planned or scheduled cardiac surgery or percutaneous coronary intervention ​procedure. ​− Planned revascularization procedure within 6 months of randomization
• ​​Sub 1: 5 Participants with a prior history of hypertensive crisis or hypertensive encephalopathy​
• ​​Sub 1: 6 Any of the following bleeding risks: ​− CT/MRI images showing tumor encircling or invading a large vascular lumen (eg, pulmonary artery or superior vena cava). ​− History of hemoptysis (≥ 2.5 mL of bright red blood per episode) within 6 months prior to randomization. ​− Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). ​− History of significant bleeding disorders or vasculitis within 6 months prior to randomization. Well-controlled hemorrhoidal bleeding is not considered significant bleeding if the condition does not pose a significant risk for use of bevacizumab as determined by investigator. ​− Major vascular disease (eg, aortic aneurysm requiring surgical repair or associated with recent peripheral artery thrombosis) within 6 months prior to randomization