Zanubrutinib and Venetoclax in CLL (ZANU-VEN)

Excluded: BTK C481X mutation

Known BTK C481X mutation.

Must have received: any anti-cancer therapy

Participants must have relapsed after at least one prior line of therapy and must currently require therapy by 2019 IWCLL criteria.

Cannot have received: covalent BTK inhibitor (ibrutinib, acalabrutinib)

Exception: Cohort A only

For enrollment to Cohort A: Participants must be covalent BTK and BCL-2 inhibitor naïve. Participants who have received prior therapy with a covalent BTK or BCL-2 inhibitor are not eligible, including but not limited to prior treatment with ibrutinib or acalabrutinib.

Cannot have received: BCL-2 inhibitor

Exception: Cohort A only

For enrollment to Cohort A: Participants must be covalent BTK and BCL-2 inhibitor naïve.

Cannot have received: BTK inhibitor and BCL-2 inhibitor (both)

Exception: Cohort B only

For enrollment to Cohort B: participants who have received prior treatment with both a BTK inhibitor and BCL-2 inhibitor.

Cannot have received: anti-cancer therapy

Exception: within 2 weeks of Cycle 1 Day 1; exceptions: adjuvant hormonal therapy, corticosteroid therapy (prednisone or equivalent ≤ 20 mg daily, stabilized ≥ 7 days), topical/inhaled/intra-articular/ophthalmologic corticosteroids; Cohort C may remain on prior BTK inhibitor up to 2 days prior to Cycle 1 Day 1

Participants who have had previous anti-cancer therapy (e.g., chemotherapy, radiotherapy, immunotherapy, biologic therapy, hormonal therapy, surgery, investigational agents, and/or tumor embolization) within 2 weeks of Cycle 1 Day 1 with the following exceptions: Hormonal therapy given in the adjuvant setting; Corticosteroid therapy (prednisone or equivalent ≤ 20 mg daily) is allowed as clinically warranted as long as the dose is stabilized at least for 7 days prior to initial dosing. Topical, inhaled, intra-articular, or ophthalmologic corticosteroids are permitted; Participants enrolling to Cohort C may remain on prior BTK inhibitor therapy up until 2 days prior to Cycle 1 Day 1

Cannot have received: allogeneic hematologic stem cell transplant

History of a prior allogeneic hematologic stem cell transplant.