BGB-16673-303 (CaDAnCe-303)

Adults >=18 with confirmed CLL/SLL, prior covalent BTKi exposure, indication for treatment per iwCLL, ECOG 0–2, protocol-defined organ/marrow function, reproductive safeguards, and life expectancy >6 months.

Patients are eligible only if all criteria are met: 1. Signed informed consent (patient or legal representative) and ability to comply with protocol requirements/restrictions. 2. Age >=18 years. 3. Confirmed CLL/SLL diagnosis per 2018 iwCLL criteria. 4. Prior CLL/SLL treatment with a covalent BTKi: a) Disease relapsed/refractory after at least one line including a covalent BTKi OR intolerance to covalent BTKi. b) Prior ncBTKi and/or BCL2 inhibitor allowed but not required. Notes: line of therapy is >=2 consecutive cycles of systemic anticancer regimen; BTKi-intolerant patients are not required to have >=2 cycles; patients must have had only one covalent-BTKi-containing regimen (with protocol-defined exception if initial BTKi was stopped for non-progression reasons). 5. Requires treatment based on >=1 iwCLL-related criterion/history, including need for subsequent line or persistent significant burden after prior line; progressive marrow failure (worsening anemia/thrombocytopenia); massive/progressive/symptomatic splenomegaly or lymphadenopathy; progressive lymphocytosis/LDT <6 months; poorly steroid-responsive autoimmune cytopenias; symptomatic extranodal involvement; or disease-related constitutional symptoms. 6. Measurable disease by CT/MRI for SLL (>=1 node >1.5 cm in long axis and measurable in two perpendicular diameters). Not required for CLL. 7. ECOG performance status 0-2. 8. Adequate organ function at screening: a) Bone marrow function: - ANC >=1000/mm3 (or >=750/mm3 with marrow involvement), no growth factor support within 7 days. - Platelets >=100,000/mm3 (or >=25,000/mm3 with marrow involvement), no growth factor/transfusion within 7 days. - Hemoglobin >=8.0 g/dL (or lower if due to marrow infiltration by CLL/SLL), no growth factor/transfusion within 7 days. - WBC >4000/mm3. b) eGFR >=30 mL/min (CKD-EPI 2021 equation). c) Amylase <=1.5 x ULN and lipase <=1.5 x ULN. d) AST/ALT <=3.0 x ULN and total bilirubin <=1.5 x ULN (or protocol-defined Gilbert allowance). e) INR <=1.5 x ULN and aPTT <=1.5 x ULN. 9. Women of childbearing potential: negative serum pregnancy test within 14 days pre-first dose and repeat within 24 hours pre-dose; highly effective contraception required during treatment and protocol-defined post-treatment windows. 10. Nonsterile men: highly effective contraception and no sperm donation during treatment and protocol-defined post-treatment windows. 11. Life expectancy >6 months.

Prolymphocytic leukemia/Richter transformation, recent transplant/CAR-T, severe active infection (incl TB/latent TB), active HBV/HCV/HIV criteria, major cardiovascular/QTc risk, CNS disease, prohibited prior/concomitant therapies, pregnancy/breastfeeding, severe bleeding risks.

Patients are excluded if any criterion applies: 1. Known prolymphocytic leukemia or history/suspicion of Richter transformation. 2. Prior autologous SCT (<3 months) or CAR-T (<6 months). 3. Severe allergic reaction/hypersensitivity to active ingredients/excipients of BGB-16673, bendamustine, or rituximab. 4. Life-threatening illness/organ dysfunction/profound anticoagulation need/bleeding disorder that may compromise safety or interpretation. 5. Unable to comply with protocol requirements. 6. Recent prohibited prior therapies before first dose: a) <=28 days (or 5 half-lives): biologic/immunologic anticancer therapies (including monoclonal antibodies/cancer vaccines). b) <=14 days (or 5 half-lives): systemic chemotherapy/radiation; specified Chinese patent medicines with anticancer activity. c) <=7 days (or 5 half-lives): antineoplastic-intent corticosteroids; BTKi/targeted small molecules with antineoplastic intent. 7. Antineoplastic-intent corticosteroids <=7 days pre-dose (short, protocol-defined symptom-control allowance permitted). 8. Strong CYP3A inhibitor/inducer timing violations or requirement for long-term strong CYP3A inhibitor/inducer use. 9. Current/history of CNS involvement by CLL/SLL (brain, spinal cord, leptomeninges, CSF). 10. Other malignancy within <=2 years (except protocol-allowed low-risk/curatively treated exceptions). 11. Ischemic stroke/intracranial hemorrhage within 6 months. 12. History of confirmed progressive multifocal leukoencephalopathy. 13. Active fungal, bacterial (including tuberculosis and latent tuberculosis infection), and/or viral infection requiring parenteral systemic therapy. 14. Active hepatitis B/C or HIV based on protocol-specified serologic/viral load criteria (with protocol-allowed controlled infection exceptions and monitoring). 15. Major surgery within <=28 days before first dose, without adequate recovery. 16. Unrecovered toxicity from prior anticancer therapy (>Grade 1, with protocol exceptions). 17. Prior BTK-targeted protein degrader or other BTK degradation-mechanism compound. 18. Clinically significant cardiovascular disease, including recent MI, unstable angina, significant arrhythmias, NYHA III/IV CHF, QTcF >480 msec, high-grade AV block without pacemaker, or uncontrolled hypertension. 19. Inability to swallow tablets or significant GI dysfunction affecting absorption. 20. Pregnant or breastfeeding female. 21. Requirement for warfarin or other vitamin K antagonists. 22. Severe bleeding disorder history (e.g., hemophilia A/B, von Willebrand disease, spontaneous severe bleeding requiring intervention). 23. Live vaccine <=28 days before first dose (with protocol exceptions for non-live vaccines). 24. Concurrent participation in another therapeutic interventional study. 25. Medical/psychiatric/substance-use condition likely to impair safety/compliance or confound interpretation. 26. Ongoing significant liver disease conditions as listed in protocol (e.g., drug-induced liver injury, alcoholic liver disease, NASH, cirrhosis/portal hypertension, etc.).