Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma
Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma
Screening (up to 28 days); daily treatment until disease progression, unacceptable toxicity
 or death, withdrawal of consent, lost to follow-up, or study termination from sponsor;
 treatment (up to 2 years), safety follow-up (30 days); survival follow-up until data cutoff
 for final analysis.
This is a single-arm, multicenter, open-label Phase 2 study to evaluate efficacy, safety,
 tolerability of zanubrutinib in participants with relapsed/refractory non-GCB type Diffuse
 Large B Cell Lymphoma.

 The study will enroll approximately 40 participants treated with zanubrutinib 160mg BID. All
 participants in the study will be treated until disease progression, unacceptable toxicity,
 death, withdrawal of consent, or the study is terminated by the sponsor for final analysis.
 At the time of final analysis, participants who remain on treatment will be considered for
 participation in the extension study when eligible. A treatment cycle consists of 28 days.
Key Inclusion Criteria:

 1. Histologically confirmed non-germinal center diffuse large B cell lymphoma (DLBCL), by
 immunohistochemistry using the Hans algorithm,

 1. CD10- and BCL6-,

 2. CD10-, BCL6+, but MUM1+

 2. Men and women ≥ 18 years of age.

 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

 4. Measurable disease is defined as at least 1 lymph node >1.5 cm in longest diameter and
 measurable in 2 perpendicular dimensions.

 5. All participants must provide fresh tumor biopsy or recent tumor tissue samples
 (within 2 years of study entry [informed consent form signed]).

 6. Received at least one prior therapy for DLBCL that includes anthracycline based
 chemotherapy.

 7. Participant not eligible for or refuses intensive chemotherapy and hematopoietic stem
 cell transplant.

 8. Documented failure to achieve at least partial response (PR) with, or documented
 disease progression after response to, the most recent treatment regimen.

 9. Neutrophils ≥ 1 x 109/L independent of growth factor support within 7 days of study
 entry.

 10. Platelets ≥ 75 x 109/L, independent of growth factor support or transfusion within 7
 days of study entry

 11. Creatinine clearance of ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or
 estimated glomerular filtration rate [eGFR].

 12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.

 13. Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome), then up to 5xULN allowed.

 14. Independent of erythropoietin (EPO) support or transfusion within 7 days of first dose
 of study drug.

 15. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time
 (APTT) ≤ 1.5 x ULN.

 16. Participants may be enrolled who relapse after autologous stem cell transplant if they
 are at least 6 months after transplant, participants should have no active infections
 (ie, fungal or viral).

 17. Females of childbearing potential must agree to use highly effective forms of birth
 control throughout the course of the study and at least up to 90 days after last dose
 of study drug. Highly effective forms of birth control can be defined as abstinence,
 hysterectomy, bilateral oophorectomy with no menstrual bleeding for up to 6 months,
 intrauterine contraception, hormonal methods such as contraceptive injection, oral
 contraceptive, etc. Males must have undergone sterilization-vasectomy, or utilize a
 barrier method where the female partner utilizes the effective forms of birth control
 noted above.

 18. Life expectancy of > 3 months.

 19. Able to provide written informed consent and can understand and comply with the
 requirements of the study.

 Key Exclusion Criteria:

 1. Current or history of central nervous system (CNS) lymphoma.

 2. Prior exposure to a BTK inhibitor.

 3. Prior corticosteroids (at dosages equivalent to prednisone > 20 mg/day) given with
 anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, or
 radiation therapy within 3 weeks, or antibody based therapies or Chinese anti-cancer
 herbal therapies within 4 weeks of the start of study drug.

 4. Major surgery within 4 weeks of screening.

 5. Toxicity of ≥ Grade 2 from prior anti-cancer therapy (except for alopecia, absolute
 neutrophil count (ANC) and platelets. For ANC and platelets, please follow inclusion
 criteria #9 [neutrophils] and #10 [platelets]).

 6. History of other active malignancies within 2 years of study entry, with exception of
 (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or
 squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally
 (surgery or other modality) with curative intent.

 7. Currently active clinically significant cardiovascular disease such as uncontrolled
 arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by
 the New York Heart Association (NYHA) Functional Classification, or history of
 myocardial infarction within 6 months of screening. Left Ventricular Ejection Fraction
 (LVEF) is lower than 50% measured by echocardiography (ECHO) (AHA,2016).

 8. QTcF (Fredericia's correction) > 450 msecs or other significant ECG abnormalities
 including second degree atrioventricular (AV) block Type II, or third degree AV block.

 9. Unable to swallow capsules or disease significantly affecting gastrointestinal
 function such as malabsorption syndrome, resection of the stomach or small bowel,
 symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

 10. Uncontrolled systemic infection or infection requiring parenteral anti-microbial
 therapy.

 11. Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C
 infection (detected positive by polymerase chain reaction [PCR]).

 12. Pregnant or lactating women.

 13. Any life-threatening illness, medical condition or organ system dysfunction which, in
 the investigator's opinion, could compromise the participant's safety, or put the
 study at risk.

 14. On medications which are strong cytochrome P450, family 3, subfamily A (CYP3A)
 inhibitors or CYP3A inducers

 NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.