A Study to Investigate Sonrotoclax Combined With Zanubrutinib Versus Zanubrutinib Alone in Participants With Previously Untreated Chronic Lymphocytic Leukemia

The purpose of this study is to support the registration plan of sonrotoclax plus zanubrutinib treatment in participants with previously untreated CLL. This study is designed to assess the contribution of sonrotoclax to the efficacy outcome of the combination of zanubrutinib and sonrotoclax.

This study will test how effective and safe sonrotoclax plus zanubrutinib treatment compared with zanubrutinib alone in participants with previously untreated chronic lymphocytic leukemia (CLL).

The main goals of the study are to determine how many participants may no longer have evidence of cancer or have some improvement in the signs and symptoms of cancer after treatment and to determine what adverse events, or side effects, patients might experience.

Sonrotoclax is an experimental drug that works by blocking a protein called B-cell lymphoma-2 (Bcl-2). This protein helps certain types of blood tumor cells to survive and grow. When sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. This can lead to improvements in patients with CLL disease.

Zanubrutinib is a commercialized product that works by blocking a protein called Bruton's tyrosine kinase (BTK) and controlling the activity and survival of malignant B cells. Zanubrutinib has received approval in over 65 countries/regions worldwide for the treatment of adult participants with B cell malignancies, including CLL.

The study will enroll approximately 87 participants who will be randomly assigned by a computer program to receive one of the following treatments: sonrotoclax + zanubrutinib or zanubrutinib.

The study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 5 years.

Eligibility Criteria:
Inclusion Criteria:

1. Previously untreated adult patient ≥ 18 years with a confirmed diagnosis of CLL.
2. CLL requiring treatment as per pre-defined criteria.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2.
4. Measurable disease by CT/MRI.
5. Adequate marrow function.
6. Adequate liver function as indicated by aspartate aminotransferase (AST) alanine aminotransferase (ALT) and serum total bilirubin.
7. Adequate renal function.
8. Life expectancy \> 6 months.
9. Signed informed consent and able to comply with the study protocol in the investigator's judgment.
10. Women of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 90 days after the last dose of study drug.

Exclusion Criteria:

1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
2. Known central nervous system involvement
3. Received previous systemic treatment for CLL
4. Clinically significant cardiovascular disease
5. Severe or debilitating pulmonary disease
6. History of prior malignancy
7. Active fungal, bacterial, and/or viral infection requiring systemic therapy
8. Positive HIV serology (HIVAb) status or serologic status reflecting active hepatitis B or C infection
9. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment
10. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
11. History of stroke or intracranial hemorrhage ≤ 6 months before the first dose of study treatment
12. Unable to swallow capsules or tablets or diseases significantly affecting GI function
13. Hypersensitivity to zanubrutinib, sonrotoclax, or any of its excipients
14. Use of investigational agents within the last 4 weeks before screening
15. Pregnant and lactating females

Note: Other protocol defined Inclusion/Exclusion criteria may apply