A Study Comparing Zanubrutinib With Bendamustine Plus Rituximab in Participants With Previously Untreated CLL or SLL

This is a global phase 3, open label, randomized study of zanubrutinib versus bendamustine plus rituximab (B+R) in participants with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), including participants without del(17p) [Cohort 1] and participants with del(17p) [Cohort 2 and Cohort 3]. Participants in Cohort 1 are randomized 1:1 to zanubrutinib (Arm A) or bendamustine plus rituximab (Arm B). Randomization will be stratified by age, Binet stage, immunoglobulin variable region heavy chain (IGHV) mutational status, and geographic region. Participants in Cohort 2 will receive treatment with zanubrutinib. Participants in Cohort 3 will receive treatment with zanubrutinib and venetoclax.

Key Inclusion Criteria:

• Unsuitable for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR)
• Confirmed diagnosis of CD20-positive CLL or SLL, requiring treatment
• Measurable disease by imaging
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Life expectancy ≥ 6 months
• Adequate bone marrow function
• Adequate renal and hepatic function

Key Exclusion Criteria:

• Previous systemic treatment for CLL/SLL
• Requires ongoing need for corticosteroid treatment
• Known prolymphocytic leukemia or history of or suspected Richter's transformation.
• Clinically significant cardiovascular disease
• Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix of breast, or localized Gleason score 6 prostate cancer
• History of severe bleeding disorder
• History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug
• Severe or debilitating pulmonary disease
• Inability to swallow capsules or disease affecting gastrointestinal function
• Active infection requiring systemic treatment
• Known central nervous system involvement by leukemia or lymphoma
• Underlying medical condition that will render the administration of study drug hazardous or obscure interpretation of toxicity or AEs
• Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C infection
• Major surgery ≤ 4 weeks prior to start of study treatment
• Pregnant or nursing females
• Vaccination with live vaccine within 35 days prior to the first dose of study drug.
• Ongoing alcohol or drug addiction
• Known hypersensitivity to zanubrutinib, bendamustine, rituximab, or venetoclax (as applicable) or any other ingredients of the study drugs
• Requires ongoing treatment with strong cytochrome P450 (CYP3A) inhibitor or inducer
• Concurrent participation in another therapeutic clinical study

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