Selinexor, Carfilzomib, and Dexamethasone Versus Placebo, Carfilzomib, and Dexamethasone in Multiple Myeloma

This is a Phase 2, two-arm, randomized, placebo-controlled, double-blind, multicenter study
of relapsed/refractory multiple myeloma patients who have received at least two prior
therapies, including a proteasome inhibitor and an IMiD.

Patients who meet all the eligibility criteria will be randomized to one of two blinded
treatment arms:

- selinexor + carfilzomib + dexamethasone

- placebo + carfilzomib + dexamethasone

Inclusion Criteria:

- Symptomatic, histologically confirmed MM, based on IMWG guidelines. Patients must
have measurable disease as defined by at least one of the following:

- Serum M-protein ≥ 1.0 g/dL by serum protein electrophoresis (SPEP) or for
immunoglobulin (Ig) A myeloma, by quantitative IgA; or

- Urinary M-protein excretion at least 200 mg/24 hours; or

- Serum FLC ≥ 100 mg/L, provided that the serum FLC ratio is abnormal.

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

- Must have received ≥ 2 prior anti-MM therapies including a proteasome inhibitor and
an IMiD. The most recent proteasome inhibitor must not have been carfilzomib.

- Patients previously treated with carfilzomib are eligible as long as they meet the
following criteria:

- Not received carfilzomib within 6 months (183 days) of Cycle 1 Day 1 (C1D1), and

- Carfilzomib was not part of their most recent therapy for the treatment of MM,
and

- Did not discontinue carfilzomib treatment because of adverse effects.

- MM that is refractory to the most recent treatment regimen. Refractory is defined as
≤ 25% response to therapy, or progression during therapy, or progression on or within
60 days after completion of therapy.

Exclusion Criteria:

- Smoldering MM.

- Active plasma cell leukemia.

- MM that does not express M-protein or serum FLC (i.e., non-secretory MM is excluded;
plasmacytomas without M-protein or serum FLC are excluded).

- Documented active systemic amyloid light chain amyloidosis.

- Active MM involving the central nervous system.

- Active polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin
changes (POEMS) syndrome.

- Prior autologous stem cell transplantation < 1 month or allogenic stem cell
transplantation < 3 months prior to C1D1.

- Active graft versus host disease (after allogeneic stem cell transplantation) at
C1D1.