BGB-16673-303 (CaDAnCe-303)

R/R CLL/SLL requiring treatment per iwCLL 2018 criteria with documented prior exposure to a covalent BTK inhibitor.

1. Confirmed diagnosis of CLL or SLL meeting iwCLL 2018 criteria. 2. Previously treated with at least 1 regimen containing a covalent BTK inhibitor (cBTKi) (eg, ibrutinib, acalabrutinib, or zanubrutinib) for CLL/SLL. 3. Documented failure of cBTKi therapy defined as disease progression during or after cBTKi therapy, or intolerance of cBTKi therapy (defined as having discontinued cBTKi due to 1 or more adverse events [AEs]). 4. Active disease meeting at least 1 of the following iwCLL 2018 criteria for requiring treatment: a. Evidence of progressive marrow failure as desired by the development of, or worsening of, anemia and/or thrombocytopenia. b. Massive (ie, >= 6 cm below the left costal margin) or progressive or symptomatic splenomegaly. c. Massive nodes (ie, >= 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. d. Progressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of ALC obtained intervals of 2 weeks over a 2- to 3-month observation period. In patients with initial ALC < 30 \times 10^9/L, LDT should not be used as a single parameter to define a treatment indication. e. At least one of the following disease-related symptoms: i. Unintentional weight loss >= 10% within the previous 6 months. ii. Significant fatigue (ie, ECOG PS 2 or worse; inability to work or perform usual activities). iii. Fevers >= 38.0^C for 2 or more weeks without evidence of infection. iv. Night sweats for more than 1 month without evidence of infection. 5. For SLL patients only, measurable disease as defined by at least 1 lymph node > 1.5 cm in the longest diameter. 6. ECOG PS of 0, 1, or 2. 7. Adequate organ function: a. ANC >= 1000/mm^3 (unless due to marrow involvement by CLL/SLL, in which case ANC >= 750/mm^3). b. Platelet count >= 100,000/mm^3 (unless due to marrow involvement by CLL/SLL, in which case platelet count >= 25,000/mm^3). c. Hemoglobin >= 8.0 g/dL. d. eGFR >= 30 mL/min. e. AST and ALT <= 3 \times ULN. f. Total bilirubin <= 1.5 \times ULN (unless documented Gilbert’s syndrome).

Known or suspected Richter’s Transformation, history of central nervous system involvement, or prior treatment with any BTK-targeted protein degrader.

1. History of or suspected Richter’s transformation or prolymphocytic leukemia. 2. Current or history of CLL/SLL involvement of the central nervous system (CNS) (ie, brain, spinal cord, or cerebrospinal fluid). 3. Prior treatment with any BTK-targeted protein degrader. 4. Prior autologous SCT within 3 months or CAR-T cell therapy within 6 months of the first dose of study drug. 5. Prior allogeneic SCT (for specific substudies/cohorts). 6. Clinically significant cardiovascular disease: a. Myocardial infarction or unstable angina within 6 months. b. History of clinically significant arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, Torsades de Pointes). c. NYHA Class III or IV congestive heart failure. d. Mean QTcF > 480 ms based on triplicate ECGs. 7. Active infection requiring parenteral systemic therapy. 8. Known HIV infection. 9. Active HBV or HCV infection: a. HBsAg positive. b. HBsAg negative but HBcAb positive with detectable HBV DNA. c. HCV RNA positive. 10. History of ischemic stroke or intracranial hemorrhage within 6 months. 11. Treatment with a strong CYP3A inhibitor or inducer within 5 half-lives or 14 days of the first dose of study drug. 12. Use of warfarin or other vitamin K antagonists. 13. Received a live vaccine within 28 days of the first dose of study drug.