A Study to Evaluate Efficacy and Safety of Zanubrutinib With R-CHOP in Newly Diagnosed Non-GCB DLBCL Patients With Double Expression

Inclusion Criteria:

* Subject must be 18 years of age or older.
* No prior treatment for DLBCL.
* Histologically - confirmed non-GCB subtype.
* MYC+≥40% and BCL2+≥50% by IHC
* Lesions must be measurable. A measurable node lesion must have a longest diameter greater than 1.5 cm. A measurable extra-nodal lesion should have a longest diameter greater than 1.0 cm.
* Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2
* Stage II (not candidates for local X-ray therapy), III, or IV disease by the Ann Arbor Classification
* Hematology values must be within the following limits at baseline:

  * Neutrophils ≥ 1 x 109/L, independent of growth factor support within 7 days of initiation of the combination therapy.
  * Platelets ≥ 75x 109/L, independent of growth factor support or transfusion within 7 days of initiation of the combination therapy. (platelets≥ 50 x 109/L, if there is bone marrow involvement.)
* Biochemical values must be within the following limits at baseline:

  * Alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN). Aspartate aminotransferase (AST) ≤3 x ULN.
  * Total bilirubin ≤1.5 x ULN, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
  * Serum creatinine ≤2 x ULN or estimated Glomerular Filtration Rate≥40 mL/min/1.73m2
* International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 x ULN.

Able to provide written informed consent, can understand and comply breastfeeding are ineligible for this study.

Exclusion Criteria:

* Primary mediastinal lymphoma.
* Central nervous system involvement lymphoma.
* Histologically transformed lymphoma.
* Diagnosed or treated for malignancies other than DLBCL.
* History of stroke or intracranial hemorrhage within 6 months.
* Major surgery within 4 weeks.
* Required ongoing treatment with medication that are strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong/median effect CYP3A inducers.
* Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification, or Echocardiography: Left ventricular ejection fraction (LVEF) \< 50%
* Active, clinically significant Electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block Type II, or third-degree AV block or QT interval corrected for heart rate (QTcF) prolongation, defined as a QTcF \> 450 msec.
* Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
* Known human immunodeficiency virus (HIV) infection, or active hepatitis B or hepatitis C infection.
* Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of zanubrutinib capsules, or put the study outcomes at undue risk.

Pregnant or lactating women.