BTK inhibitors and BCL-2 inhibitors have demonstrated significant clinical activity in mature B-cell malignancies, and combination therapy may provide improved clinical benefit. This is a multi-center, open-label, single-arm Phase Ib/II clinical study. The purpose of this clinical trial is to investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of Rocbrutinib, a fourth-generation Bruton tyrosine kinase inhibitor (BTKi), in combination with the BCL-2 inhibitor Lacutoclax in patients with mature B-cell malignancies. The Phase Ib will use a classic 3+3 dose-escalation design to evaluate dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD), and identify the recommended dosing regimen. The Phase II portion is intended to further evaluate the efficacy and safety of the combination therapy.

Inclusion Criteria:

1. Age ≥18 years, regardless of sex.

2. Ib: Histologically confirmed diagnosis of CLL/SLL (per 2018 iwCLL criteria) or B-cell malignancies (per 2022 WHO classification), including: MCL, DLBCL, FL, and WM. Must have received at least one prior line of systemic therapy, with documented disease progression or intolerance.

   II: For Treatment-naïve (TN) CLL/SLL patients: Must meet iwCLL treatment indications and no prior systemic therapy. For R/R CLL/SLL patients: at least one prior systemic therapy with documented disease progression or intolerance.

3. Have at least one measurable lesion.

4. Phase Ib: ECOG performance status ≤1; phase II: ECOG performance status ≤2.

5. Life expectancy ≥ 12 weeks.

6. Adequate coagulation function, liver and kidney function, bone marrow hematopoietic function.

7. Male patients and female patients of childbearing potential must agree to use effective contraception during the study and for 90 days after the last dose of study treatment. Female patients of childbearing potential must have a negative pregnancy test before study treatment and must not be breastfeeding. Male patients must not donate sperm during the study and for 90 days after the last dose.

8. Participation is voluntary, requiring signed informed consent and compliance with the treatment regimen and visit schedule.

Exclusion Criteria:

1. Known hypersensitivity or intolerance to Rocbrutinib, Lacutoclax, or any of their excipients; prior treatment with any BCL-2 inhibitor; or prior treatment with both covalent and non-covalent BTK inhibitors.
2. Use of systemic corticosteroids at doses equivalent to >20 mg/day of prednisone for ≥3 days within 7 days prior to the first dose.
3. History of or currently suspected Richter's syndrome.
4. Known or suspected central nervous system (CNS) involvement.
5. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT), or autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy within 90 days before the first dose of study treatment.
6. Received antitumor therapy, investigational agents, major surgery, severe trauma, or live attenuated vaccines within 4 weeks or 5 half-lives prior to the first dose of study treatment.
7. Received herbal medicines for antitumor treatment, or localized radiotherapy within 14 days prior to the first dose of study treatment.
8. Use of moderate or strong CYP3A inhibitors within 7 days prior to the first dose of study treatment, or consumption of grapefruit, grapefruit juice, starfruit, or Seville oranges within 3 days prior to prior to the first dose.
9. History of other active malignancies within the past 3 years, except for curatively treated basal cell carcinoma, localized squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other malignancies considered cured.
10. Any severe and/or uncontrolled systemic disease, or any other condition that, in the opinion of the investigator, makes the patient unsuitable for participation in the study.
11. Any of the following events within 6 months prior to the first dose: Symptomatic arrhythmia, myocardial infarction, intracranial hemorrhage, or Stroke.
12. Impaired cardiac function.
13. Any uncontrolled systemic infection.
14. Conditions that may impair oral drug administration or significantly affect absorption or pharmacokinetics of the study drug.
15. Unable to discontinue moderate or strong CYP3A inhibitors or inducers, P-gp (P-glycoprotein) inhibitors, sensitive substrates of OATP1B3 or CYP2C8 during the study period.
16. Received vaccination with any live-attenuated vaccines within 4 weeks prior to the first dose of study treatment.
17. Evidence of an active bleeding constitution or a history of significant hemorrhagic disorders.
18. Requirement for ongoing therapy with warfarin or other vitamin K antagonists.
19. Presence of an active, uncontrolled, or symptomatic autoimmune disease that requires systemic treatment.
20. Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.