Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab

Main Inclusion Criteria:

1. Participant must be ≥ 18 years at the time of signing informed consent.
2. Diagnosis of CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018)
3. Participants must have received first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ PR (i.e., CR, CRi, nPR, or PR) with a minimum of 2 years since the end of the prior 1L treatment.
4. The following data must be available or at least the appropriate samples drawn/acquired prior to dosing:

   1. IGHV (mutated vs. unmutated)
   2. del(17p) (present or absent)
   3. TP53 mutation (present or absent)
5. ECOG performance status 0, 1 or 2
6. Adequate organ and bone marrow (BM) function.

Main Exclusion Criteria:

1. Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.
2. Significant cardiovascular or cerebrovascular disease.
3. Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
4. Child-Pugh B/C liver cirrhosis.
5. History of prior or current malignancy.
6. HIV positive
7. History of progressive multifocal leukoencephalopathy (PML).
8. Active hepatitis B or C infection:
9. Corticosteroid use \> 20 mg within 1 week before the first dose of study intervention.
10. History of hypersensitivity or anaphylaxis to study intervention(s).
11. Requires treatment with a strong CYP3A4 inhibitor/inducer.
12. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
13. Major surgical procedure within 30 days of the first dose of study intervention.