A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia

This is a global, Phase 3, randomized study of zanubrutinib versus ibrutinib in approximately
400 patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic
lymphoma.

The primary efficacy endpoint is overall response rate determined by independent central
review. Patients will be randomized in a 1:1 manner to either zanubrutinib or ibrutinib.
Treatment with zanubrutinib and ibrutinib will be open label.

Inclusion Criteria

1. Age 18 years or older

2. Confirmed diagnosis of CLL or SLL that meets the 2008 IWCLL criteria

3. CLL/SLL requiring treatment per 2008 IWCLL criteria

4. Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL

5. Measurable disease by CT/magnetic resonance imaging (MRI)

6. ECOG performance status of 0, 1, or 2

7. Life expectancy ≥ 6 months

8. Adequate bone marrow function

9. Adequate renal and hepatic function

Exclusion Criteria

1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's
transformation

2. Clinically significant cardiovascular disease.

3. Prior malignancy within the past 3 years, except for curatively treated basal or
squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the
cervix or breast

4. History of severe bleeding disorder or history of spontaneous bleeding requiring blood
transfusion or other medical intervention

5. History of stroke or intracranial hemorrhage within 180 days before first dose of
study drug

6. Severe or debilitating pulmonary disease

7. Active fungal, bacterial, and/or viral infection requiring systemic therapy

8. Known central nervous system involvement by leukemia or lymphoma

9. Known infection with HIV or active viral hepatitis B or C infection

10. Moderate or severe hepatic impairment, ie, Child-Pugh class B or C

11. Major surgery within 4 weeks of the first dose of study drug

12. Prior treatment with a BTK inhibitor

13. Toxicity from prior anticancer therapy that has not recovered to ≤ Grade 1

14. Pregnant or lactating women

15. Vaccination with a live vaccine within 35 days prior to the first dose of study drug

16. Hypersensitivity to zanubrutinib, ibrutinib, or any of the other ingredients in either
drug

17. Concurrent participation in another therapeutic clinical trial