⁃ \- Signed, informed consent

• Ability and willingness to comply with the requirements of the study protocol

• Age ≥18 years

• Diagnosis of the following histories according to the WHO criteria

∙ CLL or SLL

‣ MCL

• For patients with SLL, peripheral blood flow cytometry must be positive with CLL-like cells accounting for at least 1% of circulating WBC.

• No prior systemic therapy for disease under study except:

∙ prior local radiation for symptomatic disease is permitted

‣ Short course systemic corticosteroids is permissible for disease control, improvement of performance status or non-cancer indication (must be ≤ 14 days and \< 100 mg/day prednisone or ≤ 20 mg/day dexamethasone). Steroids must be discontinued prior to study treatment. Inhaled steroids for asthma, topical steroids, and replacement/Stress corticosteroids are permitted. Low-dose steroids for ITP are also permitted up to the equivalent prednisone 20mg/daily at time of eligibility review.

• ECOG performance status of 0 to 2

• Adequate hematologic parameters unless due to disease under study:

∙ Absolute neutrophil count (ANC) ≥1.0 x 109/L unless neutropenia is clearly due to disease under study (per investigator discretion)

‣ Platelet count ≥ 75,000/mm3 - OR - Platelet count ≥ 20,000/mm3 if thrombocytopenia is clearly due to disease under study (per investigator discretion)

‣ Hemoglobin ≥9.0 g/dL unless anemia is clearly due to marrow involvement due to disease under study (per investigator discretion)

• Adequate renal and hepatic function, per laboratory reference range at Screening as follows:

• a. AST/SGOT, ALT/SGPT ≤2.0 x ULN b. Total bilirubin ≤ 2.0 x ULN unless:

• i. Considered secondary to Gilberts syndrome, in which case ≤3 x ULN ii. Considered due to disease under study (Per PI or Co-PI discretion)

• c. Creatinine clearance of eGFR\>30 mL/min according to the Cockcroft-Gault Equation

• For females of childbearing potential, a negative serum pregnancy test within 7 days of study treatment

• For female patients of childbearing potential, agreement to use highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\<1% per year\] when used consistently and correctly) or remain abstinent (refrain from heterosexual intercourse) during the treatment period and to continue its use for 90 days after the last dose of zanubrutinib AND 30 days after the last dose of venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)

⁃ A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\>/= 12 continuous months of amenorrhea with no identified cause other than menopause), and it not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Mullerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.

⁃ Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method.

⁃ The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

∙ For men with a female partner of childbearing potential or a pregnant female partnet: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom during the treatment period and to continue its use for 90 days after the last dose of zanubrutinib, or venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)

⁃ The reliability of sexual abstinence should be evaluated in relation duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception - Willingness to not donate or bank sperm or oocytes during the entire study treatment period and after treatment discontinuation for 90 days after the last dose of zanubrutinib AND 30 days after the last dose of venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)

⁃ Additional Eligibility Criteria for CLL Cohort:

⁃ 1\. Diagnosis of untreated CLL or SLL according to WHO criteria 2. For patients with SLL, peripheral blood flow cytometry must be positive with CLL-like cells accounting for at least 1% of circulating WBC 3. No prior systemic therapy for CLL: prior single site of local radiation for symptomatic disease is permitted 4. Subject requires treatment according to IWCLL guidelines (See Appendix A)

⁃ Additional Eligibility Criteria for TP53 Mutant MCL cohorts:

⁃ 1\. Diagnosis of untreated stage II-IV mantle cell lymphoma

⁃ a. Prior radiotherapy for localized disease is permitted 2. Presence of TP53 mutation irrespective of variant allele frequency (TP53 cohort)

⁃ OR

⁃ Presence of p53 overexpression by immunohistochemistry defined as strong nuclear staining of \>30% positive nuclei.

⁃ Additional Eligibility Criteria for Transplant Ineligible MCL cohort:

⁃ Diagnosis of untreated stage II-IV mantle cell lymphoma

• Prior radiotherapy for localized disease is permitted

⁃ Patients must meet one of the following criteria (a or b):

⁃ a. Age ≥65 years If age \<65 years of age, then patients must be ineligible for HDT/ASCT on the basis of comorbidity or organ dysfunction.

⁃ Specifically, patients must meet at least one of the following criteria below:

⁃ i.. Comorbid disease, such as CAD, CHF, pulmonary dysfunction, liver or kidney dysfunction, precluding high dose therapy secondary to expected increased morbidity and mortality. ii. ECOG 2 iii. Ejection fraction ≥35% and \<45% iv. Impaired pulmonary function test with DLCO \<50% expected v. Medical conditions which in the opinion of the treating physician in consultation with the study PI or Co-PI and DMT preclude HDT/ASCT.