Sonrotoclax, Zanubrutinib and CD20mab in Untreated MCL Patients

Inclusion Criteria:

1. Subject must be ≥ 18 years of age.

2. Subject must have a confirmed Mantle Cell Lymphoma (MCL) diagnosis according to WHO (2008) criteria.

3. Previously untreated MCL

4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.

5. Nonsterile men and women of child-bearing potential must agree to use highlyeffective contraceptives (e.g., condoms, implants, injectables, combined oralcontraceptives, intrauterine devices, sexual abstinence, or sterilized partner)while on study; this should be maintained for 90 days after the last dose of studydrug.

6. Subject must have adequate bone marrow function at Screening as follows: a.Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L (neutropenia due to marrowinfiltration may be supported by growth factors);

• b. Platelets ≥ 75,000/mm3 (or ≥ 50,000/mm3 for patients with bone marrowinvolvement of lymphoma) within 7 days

7. Subject must have adequate coagulation, renal, and hepatic function, per laboratoryreference range at Screening as follows:

8. aPTT and PT not to exceed 1.5 × the upper limit of normal (ULN); Serumcreatinine not to exceed 2 x ULN, and a calculated creatinine clearance of atleast 50 mL/min using the Cockcroft-Gault equation or a 24-hour urinecollection;

9. AST or ALT ≤ 3.0 × the upper normal limit (ULN) of institution's normal range;Bilirubin ≤ 1.5 × ULN. Subjects with documented Gilbert's Syndrome may have abilirubin > 1.5 × ULN.

10. Written informed consent form according to GCP and national regulations.

Exclusion Criteria:

1. Subject has known central nervous system involvement by MCL.

2. Prior malignancy other than MCL within the past 3 years, except for curativelytreated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma insitu of the cervix or breast, or localized Gleason score 6 prostate cancer.

3. Receiving any treatment with a moderate CYP3A4 inhibitor or strong CYP3A4 inhibitoror inducer within 2 weeks (or 5 half-lives, whichever is longer) before the firstdose of study drug or requiring long-term use of strong CYP3A4 inhibitors orinducers.

4. Prior ASCT within the last 3 months; or prior autologous chimeric antigen receptor-Tcell therapy within the last 3 months; or prior allogeneic stem cell transplantwithin the last 6 months or currently has an active graft-vs-host disease requiringthe use of immunosuppressants.

5. Major surgery within 4 weeks of screening.

6. Clinically significant cardiovascular disease including the following:

7. Myocardial infarction within 6 months before screening

8. Unstable angina within 3 months before screening

9. New York Heart Association class III or IV congestive heart failure

10. History of clinically significant arrhythmias (eg, sustained ventriculartachycardia, ventricular fibrillation)

11. QT interval corrected based on Fridericia's formula (QTcF) > 480 msec.

12. History of Mobitz II second-degree or third-degree heart block without apermanent pacemaker in place

13. Uncontrolled hypertension as indicated by a minimum of 2 consecutive bloodpressure measurements showing systolic blood pressure > 170 mmHg and diastolicblood pressure > 105 mmHg at screening.

14. Prior exposure to a BCL2 inhibitor (e.g., venetoclax/ABT-199).

15. Prior exposure to a BTK inhibitor (e.g., ibrutinib, zanubrutinib).

16. History of hypersensitivity to excipient(s) of the sonrotoclax tablet.

17. Patients with unresolved hepatitis B or C infection or known HIV-positive infection：

18. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible ifhepatitis B virus (HBV) DNA is undetectable (< 20 IU/mL), and if they arewilling to undergo monitoring for HBV reactivation.

19. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCVantibody are eligible if HCV RNA is undetectable (< 15 IU/mL), and if they arewilling to undergo monitoring for HCV reactivation.

20. Unable to swallow capsules or disease significantly affecting gastrointestinalfunction such as malabsorption syndrome, resection of the stomach or small bowel,bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial orcomplete bowel obstruction.

21. Pregnant or lactating women.

22. History of stroke or intracranial hemorrhage within 6 months before the first doseof study drug.

23. Underlying medical conditions that, in the investigator's opinion, will render theadministration of study drug hazardous or obscure the interpretation of safety orefficacy results.