Safety and Efficacy of the Combination of Tirabrutinib and Entospletinib With and Without Obinutuzumab in Adults With Chronic Lymphocytic Leukemia (CLL)

Key Inclusion Criteria:

* Documentation of relapsed or refractory CLL
* Requiring treatment per modified International Workshop on CLL (IWCLL) 2008 criteria; adults without radiographically measureable disease (defined as ≥ 1 lesion \> 1.5 centimetres (cm) in diameter as assessed by computed tomography (CT) or magnetic resonance imaging (MRI)) must have bone marrow evaluation at screening
* Adequate hematologic function: platelet count ≥ 50 × 10\^9/liter (L), neutrophil count ≥ 1 × 10\^9/L, hemoglobin ≥ 8 grams per deciliter (g/dL) unless lower values are directly attributable to documented bone marrow burden of CLL
* Creatinine clearance (CrCl) ≥ 50 milliliters per minute (mL/min)
* Total bilirubin ≤ 1.5× institutional upper limit of normal (ULN) unless attributed to Gilbert's syndrome and aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5×ULN
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
* Absence of active human immunodeficiency virus (HIV), hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection
* Satisfies the following criteria:

  * For females of childbearing potential, willingness to abstain from sexual intercourse or use a protocol-specified method of contraception as described in the study protocol
  * Males of reproductive potential who engage in sexual intercourse must agree to use protocol-specified method(s) of contraception as described in the study protocol
* Able to comply with study procedures and restrictions

Key Exclusion Criteria:

* Known transformation of CLL (ie, Richter's transformation, prolymphocytic leukemia)
* Known central nervous system (CNS) involvement
* Progression on treatment with any inhibitor of Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (BCL-2), or obinutuzumab. The treatment and disease response history of participants with prior treatment with agents in these classes should be reviewed by the sponsor or the German CLL Study Group office prior to enrollment to clarify sensitivity to these treatments
* Any treatment for CLL other than corticosteroids for symptomatic management within 28 days of the start of study treatment
* Participation on a concurrent therapeutic clinical trial unless all treatment is complete with only ongoing surveillance
* Diagnosis of or concern for progressive multifocal leukoencephalopathy
* History of myelodysplastic syndrome or another malignancy other than CLL, except for the following: any malignancy that has been in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥1 year prior to start of study therapy
* Active infection requiring systemic therapy
* Pregnant or nursing women (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment and monthly during therapy)
* Active autoimmune disease or the need for higher than prednisone 10 mg daily unless for management of CLL symptoms
* History of stroke or intracranial hemorrhage within 12 months of randomization; participants requiring therapeutic anticoagulation for any indication should be discussed with the German CLL Study Group (GCLLSG) cooperating physician and/or medical monitor prior to screening
* Anticipated chronic use of strong CYP3A4/CYP2C9 inducers, moderate CYP2C9 inducers, or strong P-gp inducers while on study; use within 2 weeks of first dose of study treatment should be avoided
* Requirement for proton pump inhibitor (PPI) therapy
* Demonstration of corrected QT (QTc) interval \> 450 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval

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