The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of
selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive
hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T)
therapy. The Phase 2 portion of the study will assess the two doses of selinexor (40
milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle),
followed by 60 mg selinexor single agent continuous therapy for those who have reached a
partial or complete response. The Phase 3 portion of the study will evaluate the selected
dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6
cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous
therapy for those who have reached partial or complete response.
- Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously
diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade
lymphoma 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 2 prior lines of systemic therapy for the
treatment of DLBCL (Documentation to be provided).
- Salvage chemoimmunotherapy followed by stem cell transplantation will be considered 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 1 line of
- Positron emission tomography (PET) positive measurable disease with at least 1 node
having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal
lesion with LDi >1 cm (per the Lugano Criteria 2014) (Documentation to be provided).
- Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria
determined by the treating physician. Patients who cannot receive HSCT due to active
disease are allowed on study (up to 10 percent [%] of patients enrolled in each
Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy
must be provided by the treating physician.
- Adequate bone marrow function at screening, defined as (Documentation to be provided):
- Absolute neutrophil count (ANC) ≥1*10^9 per liter (/L).
- Platelet count ≥100*10^9/L (without platelet transfusion less than [<] 14 days prior
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 (Documentation to be provided):
- Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5*upper limit of normal
(ULN), or ≤5*ULN in cases with known lymphoma involvement in the liver.
- Serum total bilirubin ≤2*ULN, or ≤5*ULN if due to Gilbert syndrome or in cases with
known lymphoma involvement in the liver.
- Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on
- 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 6
months after ending first-line treatment, will be allowed in the study (up to 20% of
enrolled patients in each Phase).
- Agree to effective contraception during the duration of the study with contraception
use for 14 months for female patients and 11 months for male patients after the last
dose of study treatment.
- Female patients of childbearing potential must have a negative serum pregnancy test at
Screening and agree to use highly effective methods of contraception throughout the
study and for 14 months following the last dose of study treatment (except patients
with Non-Childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year,
or previous bilateral salpingo-oophorectomy, or hysterectomy).
- Male patients who are sexually active must use highly effective methods of
contraception throughout the study and for 11 months following the last dose of study
treatment. Male patients must agree not to donate sperm during the study treatment
period and for 11 months following the last dose of study treatment.
- DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma
(Hodgkin's lymphoma + non-Hodgkin's lymphoma [NHL]), DLBCL transformed from diseases
other 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 of
- Use of any standard or experimental anti-DLBCL therapy (including nonpalliative
radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer
therapy) <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 Criteria for
Adverse Events [CTCAE], v.5.0), or returned to baseline, related to the previous DLBCL
therapy, except alopecia.
- Major surgery <14 days of Cycle 1 Day 1.
- Autologous stem cell transplant (SCT) <100 days or allogeneic-SCT <180 days prior to
C1D1 or active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot
discontinue GVHD treatment or prophylaxis) or CAR-T cell infusion <90 days prior to
- 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 being compliant
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, hepatitis C or HIV infections. Patient with a history
of hepatitis B, hepatitis C or HIV are allowed under the following conditions: Patient
with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B
has been given for >8 weeks and viral load is <100 International units (IU)/mL prior
to first dose of study treatment. Patient with untreated hepatitis C virus (HCV) are
allowed if there is documentation of negative viral load per institutional standard.
Patient with human immunodeficiency virus (HIV) who have CD4+ T-cell counts ≥350
cells/microliter (µL), negative viral load per institutional standard, and no history
of acquired immune deficiency syndrome (AIDS) -defining opportunistic infections in
the last year are allowed.
- 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 ideal