Selinexor in Initial or Relapsed/Refractory Richter's Transformation

Multi-center, Phase 2, single arm, open-label study of oral selinexor monotherapy in patients
with Richter's transformation, arising in the setting of prior CLL, documented by
histologically confirmed lymphoma, including diffuse large B-cell (DLBCL) and immunoblastic
variants. Eligible patients must have had at least one prior regimen for CLL. Approximately
50 patients are anticipated to be treated in this study. Eligible patients following
screening will receive selinexor orally twice weekly (e.g., Monday and Wednesday or Tuesday
and Thursday) at a dose of 60 mg. The selinexor dose may be increased to 80 mg after Cycle 1
unless clinically contraindicated. Patients may continue in multiple treatment cycles at a
given dose; there is no maximum treatment duration. Each cycle is 28 days. Dose adjustments
will be made as appropriate by the investigator.

Inclusion Criteria:

- Richter's transformation, arising in the setting of prior CLL, documented by
histologically confirmed lymphoma, including large B-cell and immunoblastic variants.

- All patients must have received at least one prior regimen for CLL, including
cytotoxic chemotherapy, anti-CD20 monoclonal antibodies, a BTK inhibitor, or a PI3K
inhibitor. Patients may have received high dose chemotherapy/autologous stem cell
transplant (HDT/ASCT) or allogeneic hematopoietic stem cell transplant (allo SCT).

- One or more measurable (> 1.5 cm in longest dimension) disease sites on CT (preferably
PET/CT) or, if CT is contraindicated, MRI (preferably PET/MRI) scans.

- Objective documented evidence of disease progression at study entry

- ECOG status of ≤ 2

Exclusion Criteria:

- Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks
prior to Cycle 1 Day 1, except ibrutinib which may be continued until one day prior to
initiation of selinexor; radio-immunotherapy 4 weeks prior to Cycle 1 Day 1. Patients
must have recovered to Grade ≤ 1 from clinically significant adverse effects.

- Prolymphocytic transformation

- Less than 1 month since completion of autologous stem cell transplantation or less
than 3 months since completion of allogeneic stem cell transplantation

- Major surgery within 4 weeks of C1D1

- Impairment of GI function or GI disease that could interfere with the absorption of
selinexor, including obstructed GI tract and uncontrolled vomiting or diarrhea.

- Inability or unwillingness to take supportive medications including a centrally acting
appetite stimulant (e.g., mirtazapine or olanzapine) and a peripherally acting
appetite stimulant (e.g., low dose glucocorticoids or megesterol acetate).