Selinexor Treatment of Refractory Myeloma

This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus
dexamethasone 20 mg (Sd), both dosed twice weekly in each four-week cycle, in patients with
MM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and
daratumumab and refractory to prior treatment with glucocorticoids, an immunomodulatory agent
(IMiD), a proteasome inhibitor (PI), and daratumumab.

This study consists of two parts:

- Part 1 enrolled patients with both quad-refractory MM and penta-refractory MM.

- Part 2 will enroll patients with penta-refractory MM only.

Inclusion Criteria:

Measurable MM based on modified IMWG guidelines. Defined by at least one of the following:

1. Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by
quantitative IgA

2. Urinary M-protein excretion ≥ 200 mg/24 hours

3. Free Light Chain (FLC) ≥ 100 mg/L, provided that the FLC ratio is abnormal

4. If serum protein electrophoresis is felt to be unreliable for routine M-protein
measurement, then quantitative Ig levels by nephelometry or turbidimetry are
acceptable

- Must have previously received ≥ 3 anti-MM regimens including: an alkylating
agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a
glucocorticoid. There is no upper limit on the number of prior therapies provided
that all other inclusion/exclusion criteria are met.

- MM refractory to previous treatment with one or more glucocorticoids, parenteral
PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or
pomalidomide), and the anti-CD38 mAb, daratumumab. Refractory is defined as ≤ 25%
response to therapy, or progression during therapy or progression within 60 days
after completion of therapy.

Exclusion Criteria:

- Active smoldering MM.

- Active plasma cell leukemia.

- Documented systemic amyloid light chain amyloidosis.

- Active CNS MM.