SHS_492315 BENW CKPT 15267

A Phase 1b/2 Study of Selinexor (KPT-330) in Combination With Backbone Treatments for Relapsed/Refractory Multiple Myeloma

This study will independently assess the efficacy and safety of two combination therapies for the treatment of patients with relapsed/refractory multiple myeloma (RR MM): selinexor + dexamethasone + pomalidomide (SdP) and selinexor + dexamethasone + bortezomib (SdB). This is a multi-center, open-label, randomized (for dose schedule) clinical study with dose escalation (Phase 1) and expansion (Phase 2) stages to independently assess the maximum tolerated dose (MTD,) efficacy, and safety of selinexor + dexamethasone + pomalidomide (SdP), selinexor + dexamethasone + bortezomib (SdB), and selinexor + dexamethasone + lenalidomide (SdL), in patients with relapsed/refractory multiple myeloma (RR MM).

Select Inclusion Criteria (see protocol for more details):

Histologically confirmed diagnosis, measurable disease and evidence of disease progression of multiple myeloma (MM)
Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease as defined by at least one of the following (listed)
Any non-hematological toxicities must have resolved
Adequate hepatic function
Adequate renal function
Adequate hematopoietic function
SdP (Arm 1) Only: Relapsed and refractory MM with documented evidence of PD after achieving at least SD for ≥ 1 cycle during a previous MM regimen; ≤ 25% response or PD during or within 60 days from the end of the most recent MM regimen; previously undergone ≥ 2 cycles of lenalidomide and a proteasome inhibitor
SdB (Arm 2) Only: Relapsed or refractory MM with documented evidence of relapse after ≥ 1 previous line of therapy; not refractory to bortezomib in their most recent line of therapy
SdL (Arm 3) Only patients who received ≥ 1 prior therapeutic regimen (prior lenalidomide is allowed as long as patient was not refractory to prior lenalidomide)

Select Exclusion Criteria (see protocol for more details):

Smoldering MM.
MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead
Documented active systemic amyloid light chain amyloidosis
Active MM involving the central nervous system (CNS)
Active plasma cell leukemia
Blood (or blood product) transfusions and blood growth factors within 7 days of C1 D1 only for patients enrolling into the Expansion Phase
Radiation, chemotherapy, or immunotherapy or any other anticancer therapy
Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1 D1
Prior autologous stem cell transplantation < 1 month, or allogeneic stem cell transplantation < 3 months prior to C1 D1
Active graft versus host disease after allogeneic stem cell transplantation
A life expectancy of < 3 months
Major surgery within 4 weeks prior to C1 D1
Active, unstable cardiovascular function
Uncontrolled active hypertension
Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
Known active hepatitis A, B, or C
Known HIV infection or HIV seropositivity
Prior history of malignancies
Any active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of study treatment
Hypersensitivity to any of the treatments for the Arm in which the patient is enrolled
Phase I/II
NCT02343042
Cancer
Hematologic
William Bensinger, M.D.
Karyopharm
Tenzin Tsomo
  • Swedish Medical Center