Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab

Inclusion Criteria 1. Subject must be able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures. 2. Subject must be ≥ 18 years of age. 3. Subject must have confirmed diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines. a. Please note, participants with SLL must have identifiable B-cells in peripheral blood or bone marrow consistent with CLL/SLL immuno-phenotype, based on flow-cytometry, in order to be enrolled 4. Subject must have indications for treatment per the 2018 iwCLL Guidelines. 5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2. 6. Subject must have adequate organ function defined as: 1. Creatinine clearance ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or the Modification of Diet in Renal Disease equation, or as measured by nuclear medicine scan or 24-hour urine collection). 2. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 2.5 × upper limit of normal (ULN) unless due to CLL/SLL. 3. Serum total bilirubin \< 3.0 × ULN (unless documented Gilbert's syndrome) 7. Subject must have adequate bone marrow function and meet the below thresholds unless approved by sponsor if cytopenias are felt to be due to significant marrow involvement of CLL: 1. Absolute neutrophil count ≥ 1.0 x103/μL 2. Hemoglobin ≥ 7 g/dL (can be transfused up to 1 week prior to study enrollment) 3. Platelets ≥ 75,000 cells/μL OR platelets ≥ 30,000 cells/μL if clearly due to disease under study (per investigator discretion) 8. Subjects of childbearing potential must be willing to comply with pregnancy prevention interventions (as defined in Section 4.4) Exclusion Criteria A subject will be ineligible for the study if he/she meets the following criteria: 1. Previous exposure to any systemic anti-cancer therapy as a treatment for CLL/SLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, hormone therapy (other than contraceptives, hormone-replacement therapy or megestrol acetate) or investigational therapy. 2. Subject with a history of malignancy except for non-melanoma skin cancers. Subjects treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 35 years from treatment end will be allowed to enroll. Adjuvant hormonal therapy will be allowed at time of enrollment if the subject otherwise is not excluded by the 3-year waiting period. 3. Subject requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry. 4. Subjects with active autoimmune hemolytic anemia or immune thrombocytopenia purpura. 5. Subject with prolymphocytic leukemia or Richter's Transformation. 6. Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease). 7. Subject requires warfarin or equivalent vitamin K antagonist. 8. Uncontrolled or active significant infection requiring systemic treatment, subjects are eligible if they have completed antibiotic therapy 2 weeks prior to study enrollment. 9. History of suspected or confirmed PML 10. Clinically significant cardiovascular disease including the following: 1. Myocardial infarction within 6 months before screening. 2. Unstable angina within 3 months before screening. 3. New York Heart Association class III or IV congestive heart failure 4. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes). 5. QT interval corrected with Fridericia's formula (QTcF) \> 480 milliseconds based on Fridericia's formula. 6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place. 7. Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \> 170 mmHg and diastolic blood pressure \> 105 mmHg at screening. 11. Patients with stroke or CNS hemorrhage within 6 months. 12. Pregnant or breastfeeding. 14\. Major surgical procedure within 28 days of first dose of study drug. If a subject had surgery, they must have recovered adequately from any toxicity or complications before the first dose of study drug. 15\. Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication. 16\. Subject is known to be positive for human immunodeficiency virus (HIV). 17. Active hepatitis C, as confirmed by being positive for Hep C RNA by PCR. 18. Active hepatitis B infection documented by a positive PCR for Hep B DNA. If hepatitis B serology is positive for hepatitis B core antibody, but Hep B DNA PCR is negative, patient is eligible to enroll. 19\. Subject requires: 1. Strong and moderate CYP3A inhibitors within 7 days prior to the initiation of study treatment. 2. Strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment. 3. Steroid therapy for anti-neoplastic intent with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids within 7 days prior to the first dose of study drug administration. 4. Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug and throughout venetoclax administration. 20\. Known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or any of the excipients, including serum sickness with prior obinutuzumab use. 21\. Vaccination with live vaccine ≤28 days prior to start of treatment.