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

Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Selinexor (KPT-330), Carfilzomib, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma Previously Treated With a Proteasome Inhibitor and an Immunomodulatory Drug

Double-blind study will compare the efficacy and assess safety of selinexor plus carfilzomib (Kyprolis®) plus low-dose dexamethasone versus placebo plus carfilzomib plus low-dose dexamethasone in patients with relapsed/refractory 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.