A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) with or Without Selinexor in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma

Inclusion Criteria:

• Have pathologically confirmed de novo DLBCL or DLBCL transformed from previouslydiagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-gradelymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided).

• Have received at least 1 but no more than 3 prior lines of systemic therapy for thetreatment of DLBCL with relapsed or refractory disease following their most recentregimen.

• Salvage chemoimmunotherapy followed by stem cell transplantation will beconsidered as 1 line of systemic therapy.

• Maintenance therapy will not be counted as a separate line of systemic therapy.

• Radiation with curative intent for localized DLBCL will not be counted as 1line of systemic therapy.

• Positron emission tomography (PET) positive measurable disease with at least 1 nodehaving the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5.

• Not intended for HSCT or CAR-T cell therapy based on objective clinical criteriadetermined by the treating physician. Patients who cannot receive HSCT due to activedisease are allowed on study (up to approximately 15 percent [%] of patientsenrolled in each Phase). Documentation on lack of intention to proceed to receiveHSCT or CAR-T therapy must be provided by the treating physician.

• Adequate bone marrow function at screening, defined as:

• Absolute neutrophil count (ANC) ≥1*10^9 per liter (/L).

• Platelet count ≥100*10^9/L (without platelet transfusion less than [<] 14 daysprior to Cycle 1 Day 1 [C1D1]).

• Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion <14 days prior to C1D1).

• Circulating lymphocytes less than or equal to (≤) 50*10^9/L.

• Adequate liver and kidney function, defined as:

• Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5upper limit ofnormal (ULN), or ≤5ULN in cases with known lymphoma involvement in the liver.

• Serum total bilirubin ≤2ULN, or ≤5ULN if due to Gilbert syndrome or in caseswith known lymphoma involvement in the liver.

• Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) basedon Cockcroft-Gault formula.

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

• An estimated life expectancy of >3 months at Screening.

• Patients with primary refractory DLBCL defined as no response or relapse within 6months after ending first-line treatment, will be allowed in the study.

• Agree to highly effective contraception during the duration of the study withcontraception use continuing for 12 months after the last dose of study treatment

• Female patients of childbearing potential must have a negative serum pregnancy testat Screening and agree to use highly effective methods of contraception throughoutthe study and for 12 months following the last dose of study treatment (exceptpatients with Non-Childbearing potential: Age >50 years and naturally amenorrhoeicfor >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy).

• Male patients who are sexually active must use highly effective methods ofcontraception throughout the study and for 12 months following the last dose ofstudy treatment. Male patients must agree not to donate sperm during the studytreatment period and for 12 months following the last dose of study treatment.

Exclusion Criteria:

• DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseasesother than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL);T-cell rich large B-cell lymphoma.

• Previous treatment with selinexor or other XPO1 inhibitors.

• Contraindication to any drug contained in the combination therapy regimen (SR-GDP).

• Known active central nervous system or meningeal involvement by DLBCL at time ofScreening.

• Use of any standard or experimental anti-DLBCL therapy (including nonpalliativeradiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancertherapy) <21 days prior to C1D1 (prednisone <30 mg or equivalent is permitted;palliative radiation is permitted only if on non-target lesions).

• Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteriafor Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previousDLBCL therapy, except hematological abnormalities (as specified in the inclusioncriteria) and alopecia.

• Major surgery <14 days of Cycle 1 Day 1.

• Hematopoietic stem cell transplantation/CAR-T therapy as follows:

• Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 daysprior to C1D1

• Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannotdiscontinue GVHD treatment or prophylaxis)

• CAR-T cell infusion <90 days prior to Cycle 1

• Neuropathy Grade ≥2 (CTCAE, v.5.0).

• Any life-threatening illness, medical condition, or organ system dysfunction which,in the Investigator's opinion, could compromise the patient's safety, or beingcompliant with the study procedures.

• 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).

• Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or humanimmunodeficiency virus (HIV) infections:

• Patient with active HBV are allowed if antiviral therapy for hepatitis B hasbeen given for >8 weeks and viral load is <100 International units (IU)/mLprior to first dose of study treatment.

• Patients with known history of HCV or found to be HCV antibody positive onscreening, are allowed if there is documentation of negative viral load perinstitutional standard.

• Patients with HIV are allowed if they have a negative viral load perinstitutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year.

• Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment.

• Breastfeeding or pregnant women.

• Inability or unwillingness to sign an informed consent form (ICF).

• In the opinion of the Investigator, patient who are significantly below their idealbody weight.

• Patients who received a live attenuated vaccine within prior 28 days of the firstdose of study treatment.