Selinexor Plus R-CHOP in High-risk GCB-subtype Diffuse Large B-Cell Lymphoma

Inclusion Criteria:

• Patients must meet all of the following inclusion criteria to be eligible to enrollin this study:

1. Willing and able to written informed consent (ICF) .

2. Age ≥ 18 years and ≤ 75 years.

3. Histologically confirmed Diffuse Large B-Cell Lymphoma of the germinal centerB-cell(DLBCL) subtype by Hans.

4. Patients no prior chemotherapy or radiotherapy for DLBCL, with the exception ofno more than 5 days of treatment with glucocorticoids for symptom control.

5. International Prognostic Index score of 3-5.

6. Computed Tomography(CT)/Positron emission tomography (PET) positive measurabledisease per the Lugano Classification 2014, having at least 1 node with longestdiameter (LDi) greater than > 1.5cm or 1 extranodal lesion with LDi >1 cm.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

8. Adequate bone marrow function at Screening(Except for underlying diseases, suchas secondary hypersplenism due to bone marrow invasion or splenic invasionidentified by the investigator).

9. Absolute neutrophil count (ANC)≥1.5×109/L;

10. Platelet count (PLT) ≥100×109/L(no platelet transfusion within 14 daysprior to C1D1), or PLT≥ 75×109/L if due to lymphoma with bone marrowinvolvement.

11. Hemoglobin (HB)≥85g/L(no red blood cell transfusion within 14 days priorto C1D1).

12. Adequate hepatic and renal function:

13. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤2.0 xupper limit of normal (ULN), or AST and ALT≤5.0 x ULN(if due to lymphomainvolvement),

14. Serum total bilirubin ≤2×ULN, or Serum total bilirubin ≤5×ULN if due toGilbert syndrome or lymphoma involvement.

15. Estimated creatinine clearance ≥ 30 mL/min (calculated using the formulaof Cockroft-Gault).

16. Participants of childearing potential must agree to use highly effectivemethods of contraception during the duration of the study and following thelast dose of study treatment, female and male participants should continuecontraception for 14 and 11 months, respectively.

17. Female participants of childbearing potential must have a negative serumpregnancy test at screening(Non-Childbearing potential: Age >50 years andnaturally amenorrhoeic for >1 year, or previous bilateralsalpingo-oophorectomy, or hysterectomy).

18. Male participants must agree to avoid sperm donation during the durationof the study and 14 months following the last dose of study treatment.

Exclusion Criteria:

• Inclusion/Exclusion Criteria:

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

1. Willing and able to written informed consent (ICF) .

2. Age ≥ 18 years and ≤ 75 years.

3. Histologically confirmed Diffuse Large B-Cell Lymphoma of the germinal centerB-cell(DLBCL) subtype by Hans.

4. Patients no prior chemotherapy or radiotherapy for DLBCL, with the exception of nomore than 5 days of treatment with glucocorticoids for symptom control.

5. International Prognostic Index score of 3-5.

6. Computed Tomography(CT)/Positron emission tomography (PET) positive measurabledisease per the Lugano Classification 2014, having at least 1 node with longestdiameter (LDi) greater than > 1.5cm or 1 extranodal lesion with LDi >1 cm.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

8. Adequate bone marrow function at Screening(Except for underlying diseases, such assecondary hypersplenism due to bone marrow invasion or splenic invasion identifiedby the investigator).

9. Absolute neutrophil count (ANC)≥1.5×109/L;

10. Platelet count (PLT) ≥100×109/L(no platelet transfusion within 14 days prior toC1D1), or PLT≥ 75×109/L if due to lymphoma with bone marrow involvement.

11. Hemoglobin (HB)≥85g/L(no red blood cell transfusion within 14 days prior toC1D1).

12. Adequate hepatic and renal function:

13. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤2.0 x upperlimit of normal (ULN), or AST and ALT≤5.0 x ULN(if due to lymphomainvolvement),

14. Serum total bilirubin ≤2×ULN, or Serum total bilirubin ≤5×ULN if due to Gilbertsyndrome or lymphoma involvement.

15. Estimated creatinine clearance ≥ 30 mL/min (calculated using the formula ofCockroft-Gault).

16. Participants of childearing potential must agree to use highly effective methods ofcontraception during the duration of the study and following the last dose of studytreatment, female and male participants should continue contraception for 14 and 11months, respectively.

17. Female participants of childbearing potential must have a negative serumpregnancy test at screening(Non-Childbearing potential: Age >50 years andnaturally amenorrhoeic for >1 year, or previous bilateralsalpingo-oophorectomy, or hysterectomy).

18. Male participants must agree to avoid sperm donation during the duration of thestudy and 14 months following the last dose of study treatment.

Exclusion Criteria:

Patients who meet any of the following criteria will not be enrolled:

1. DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma; composite lymphoma (Hodgkin lymphoma + NHL); Gray zone lymphoma; DLBCL transformed from ChronicLymphocytic Leukemia (Richter Syndrome); Primary mediastinal large B-cell lymphoma (PMBCL); T-cell rich large B-cell lymphoma.

2. Known active central nervous system lymphoma or meningeal involvement at screening.Participants with a history of CNS disease treated into remission may be enrolled.The DLBCL of Testis involvement or more than two extranodal involvement.

3. Previous treatment with selinexor or other XPO1 inhibitors.

4. Contraindication to any drug contained in these regimen.

5. Major surgery <14 days of C1D1, Except for disease diagnosis.

6. Any life-threatening illness, medical condition, or organ system dysfunction which,in the Investigator's opinion, could compromise the participant's safety, or able tocomply with the study procedures.

7. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,antivirals, or antifungals within 7 days prior to first dose of study treatment;however, prophylactic use of these agents is acceptable (including parenteral).

8. Subjects with known active Hepatitis B (HB) infection, active Hepatitis C (HCV)infection or Human Immunodeficiency Virus (HIV) positivity. Participants with activehepatitis B Virus (HBV) are eligible if antiviral therapy for hepatitis B has beengiven for >8 weeks and viral load is <100 international units per milliliter (IU/mL); participants with untreated hepatitis C Virus (HCV) are eligible if viralload is negative per institutional standard; participants with humanimmunodeficiency virus (HIV) are eligible if cluster of differentiation 4 (CD4+)T-cell counts ≥350 cells per microliter (cells/μL), viral load is negative and nohistory of acquired immunodeficiency syndrome (AIDS)-defining opportunisticinfections in the last year.

9. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,antivirals, or antifungals within 7 days prior to first dose of study treatment;however, prophylactic use of these agents is acceptable (including parenteral).

10. Breastfeeding women or pregnant women.

11. In the opinion of the Investigator, participants who are below their ideal bodyweight and would be unduly impacted by changes in their weight.

12. Life expectancy of less than 6 months.