To compare efficacy between zanubrutinib versus bendamustine and rituximab in patients with previously untreated CLL/SLL, as measured by progression free survival assess by Independent Central Review.
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.
| Study Arm | Population | Intervention | Comparison | Outcome |
|---|---|---|---|---|
Cohort 1 |
TN CLL without del(17p) |
Zanubrutinib |
Bendamustine + Rituximab |
Primary Endpoint: PFS by IRC Key Secondary Endpoints: ORR, OS, DoR, safety |
Cohort 2 |
TN CLL with del(17p) |
Zanubrutinib |
None |
ORR, OS, PFS, DoR |
Cohort 3 |
TN CLL with del(17p) and/or TP53mut OR without del(17p) |
Zanubrutinib + Venetoclax |
None |
ORR (INV), PFS (INV), uMRD4 rate (<10-4 sensitivity), safety |
