Selinexor (KPT-330) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Inclusion Criteria (Parts 1 and 2):

• Written informed consent in accordance with federal, local, and institutionalguidelines. The participant must provide informed consent prior to the firstscreening procedure.

• Age greater than or equal to (≥) 18 years.

• ECOG performance status of less than or equal to (≤) 2.

• Participants should have estimated life expectancy of greater than (>) 3 months atstudy entry.

• Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformedfrom previously diagnosed indolent lymphoma (e.g., follicular lymphoma).

• Participants must have received at least 2 but no more than 5 previous systemicregimens for the treatment of their de novo or transformed DLBCL including (i) atleast 1 course of anthracycline-based chemotherapy (unless absolutelycontraindicated due to cardiac dysfunction, in which case other active agents suchas etoposide, bendamustine, or gemcitabine must have been given) and (ii) at least 1course of anti-CD20 immunotherapy (e.g., rituximab), unless contraindicated due tosevere toxicity. Participants who were considered ineligible for standardmulti-agent immunochemotherapy must have received at least 2 and no more than 5prior treatment regimens including at least 1 course of anti-CD20 antibodies andmust be approved by the Medical Monitor. Prior stem cell transplantation is allowed;induction, consolidation, stem cell collection, preparative regimen andtransplantation ± maintenance are considered a single line of therapy.

• Female participants of child-bearing potential must have a negative serum pregnancytest at screening and agree to use reliable methods of contraception for 3 monthsafter their last dose of medication. Male participants must use a reliable method ofcontraception if sexually active with a female of child-bearing potential. For bothmale and female participants, effective methods of contraception must be usedthroughout the study and for 3 months following the last dose.

Part 1 additional inclusion criteria:

• For participants whose most recent systemic anti-DLBCL therapy induced a PR or CR,at least 60 days must have elapsed since the end of that therapy. For all otherparticipants, at least 14 weeks (98 days) must have elapsed since the end of theirmost recent systemic anti-DLBCL therapy. . Palliative localized radiation within thetherapy-free interval is allowed. Non-chemotherapy maintenance will not beconsidered anti DLBCL therapy, and therefore is allowed during the therapy-freeinterval.

• Documented clinical or radiographic evidence of progressive DLBCL prior to dosing.

• Participants must have measurable disease per the revised criteria for responseassessment of lymphoma. Lymph nodes should be considered abnormal if the long axisis >1.5 centimeter (cm), regardless of the short axis. If a lymph node has a longaxis of 1.1 to 1.5 cm, it should only be considered abnormal if its short axis is >1.0. Lymph nodes ≤1.0 by ≤1.0 will not be considered abnormal for relapse or PD.

Part 2 additional inclusion criteria:

• At least 3 weeks (21 days) must have elapsed since the end of participant's most recent systemic anti-DLBCL therapy (prior to Cycle 1 Day 1). Palliative localized radiation within the therapy-free interval is allowed.Non-chemotherapy maintenance will not be considered anti-DLBCL therapy, and therefore is allowed during the therapy-free interval.

• Adequate hematopoietic function: (i) Hemoglobin ≥10.0 grams per deciliters (g/dL) within 14 days of starting therapy (participant may receive red blood cell [RBC] transfusion within 14 days).

(ii) Absolute neutrophil count ≥1000 cells/millimeter (mm^3) (use of granulocyte growth factors prior to and during the study is acceptable).

(iii) Platelet count ≥100,000/mm^3 within 14 days of starting therapy (use of platelet growth factors prior to and during the study is acceptable).

• Participants must have measurable disease per the revised criteria for responseassessment of lymphoma. Lymph nodes should be considered abnormal if the long axisis >1.5 cm, regardless of the short axis. Extranodal lesion should be consideredabnormal if the long axis is >1.0 cm.

Exclusion Criteria (Parts 1 and 2):

• Participants who are pregnant or lactating.

• Primary mediastinal (thymic) large B-cell lymphoma (PMBL)

• Participants must not be eligible for high-dose chemotherapy with autologous stemcell transplantation rescue (Investigator must provide detailed documentation forineligibility).

• Participants who have not recovered to Grade ≤1 clinically significant adverseevents, or to their baseline, from their most recent systemic anti-DLBCL therapy.

• Major surgery within 2 weeks of first dose of study treatment.

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

• Psychiatric illness or substance use that would prevent the participant from givinginformed consent or being compliant with the study procedures.

• Any of the following laboratory abnormalities:

(i) A circulating lymphocyte count of >50,000/L. (ii) Hepatic dysfunction: bilirubin >2.0 times the upper limit of normal (ULN) (except participants with Gilbert'ssyndrome: total bilirubin of >3ULN) and alanine aminotransferase (ALT) andaspartate aminotransferase (AST) >2.5 times ULN. In participants with known liverinvolvement of their DLBCL, AST and ALT >5ULN.

(iii) Severe renal dysfunction: estimated creatinine clearance of <30 mL/min, measured in 24-hour urine or calculated using the formula of Cockroft and Gault [(140-Age)Mass (kg)/(72creatinine mg/dL); multiply by 0.85 if female].

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

• Participants with active graft-versus-host disease after allogeneic stem celltransplantation. At least 4 months must have elapsed since completion of allogeneicstem cell transplantation.

• Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,antivirals, or antifungals on Cycle 1 Day 1; however, prophylactic use of theseagents is acceptable even if parenteral.

• Participants unable to swallow tablets, participants with malabsorption syndrome, orany other gastrointestinal disease or gastrointestinal dysfunction that couldinterfere with absorption of study treatment.

Part 1 additional exclusion criteria:

• For participants whose most recent systemic anti-DLBCL therapy induced a PR or CR:Radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancertherapy other than glucocorticoids <60 days or <14 weeks prior to Cycle 1 Day 1.

• Known central nervous system lymphoma or meningeal involvement.

• DLBCL with mucosa-associated lymphoid tissue [MALT] lymphoma, composite lymphoma (Hodgkin's lymphoma+NHL), or DLBCL transformed from diseases other than indolentNHL.

• Unstable cardiovascular function:

(i) Symptomatic ischemia, or (ii) Uncontrolled clinically significant conductionabnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1stdegree atrioventricular block or asymptomatic left anterior fascicular block /rightbundle branch block will not be excluded), or (iii) Congestive heart failure of NewYork Heart Association Class ≥3, or (iv) Myocardial infarction within 3 months.

• Participants with a BSA <1.4 m^2 as calculated per Dubois 1916 or Mosteller 1987.

• Any of the following laboratory abnormalities:

(i) Absolute neutrophil count (ANC) <1000 cells/mm^3 or platelet count <75,000/mm^3during screening and on Cycle 1 Day 1. Use of granulocyte-stimulating factors andplatelet growth factors prior to and during the study is acceptable.

(ii) Hematopoietic dysfunction: hemoglobin < 10.0 g/dL within 14 days of and including Cycle 1 Day 1 and/or patients receiving red blood cell (RBC) transfusion within 14 days of and including Cycle 1 Day 1.

• Participants who have been committed to an institution by official or judicialorder.

• Participants with dependency on the Sponsor, Investigator or study site.

Part 2 additional exclusion criteria:

• Participants with active HBV, HVC, or HIV infections. Participants with active HBVare allowed if antiviral therapy for hepatitis B has been given for >8 weeks andviral load is <100 International units per milliliters (IU/mL) prior to first doseof study treatment. Participants with known history of HCV or found to be HCVantibody positive on screening, are allowed if there is documentation of negativeviral load per institutional standard. Participants with HIV who have CD4+T-cellcounts ≥350 cells/microliter (mcL), negative viral load per institutional standard,and no history of acquired immune deficiency syndrome (AIDS)-defining opportunisticinfections in the last year are allowed.

• Known active central nervous system lymphoma or meningeal involvement. Participantswith a history of CNS disease treated into remission may be enrolled.

• DLBCL with MALT lymphoma, composite lymphoma (Hodgkin's lymphoma + NHL), DLBCLarising from CLL (Richter's transformation), or high-grade B-cell lymphoma.

• Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to Day 1 dosingor strong CYP3A inducers ≤14 days prior to Day 1 dosing.