A Study of Evaluating the Safety and Efficacy of ATG-010 in Relapsed Refractory Multiple Myeloma

This is a single-arm, open-label, multicenter study of ATG-010 (Selinexor) plus low dose Dexamethasone dosed twice weekly each week in four-week cycles, in patients with triple-refractory MM. The population refractory for the primary efficacy analysis will contain only patients with triple-MM enrolled. PK analysis would be performed which would contain approximately 30% of the patients enrolled. Safety analyses will be performed on the overall population of patients who received at least one dose of study drug among triple-refractory patient populations. Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be managed by standard care, or withdrawal, whichever occurs first.

Inclusion criteria

• Written informed consent in accordance with federal, local, and institutional guidelines.
• Age ≥ 18 years at the time of signing informed consent.
• Patients must have previously received including proteasome inhibitors (PI) (i.e., lenalidomide) and immunomodulatory drugs (i.e., bortezomib) and were refractory to both drugs.
• Any clinically significant non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #17) that patients experienced from treatments in previous clinical studies must have resolved to Grade ≤ 2 by Cycle 1 Day 1.
• Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN.
• Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine clearance of ≥ 20 mL/min, calculated using the formula of cockroft and gault.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Measurable MM based on IMWG guidelines.
• Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion Criterion #20 for transfusion washout periods for RBCs and platelets):

• Hemoglobin level ≥ 8.5 g/dL
• ANC ≥ 1000/mm^3
• Platelet count ≥ 75,000/mm^3 (patients in whom < 50% of bone marrow nucleated cells are plasma cells) or ≥ 50,000/mm^3 (patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells. [Platelet transfusions < 1 week prior to Cycle 1 Day 1 are prohibited (see below).]
• Female subjects of child-bearing potential must have both of the following:

• Agree to the use of two study physician-approved contraceptive methods simultaneously, or practice complete abstinence starting at the time of ICF signature, while on study medication, and 3 months following the last dose of study drug.
• Have negative serum pregnancy test result at screening.

Exclusion criteria

• The presence of any of the following will exclude a subject from enrollment:

• Active smoldering MM.
• Active plasma cell leukemia.
• Documented systemic amyloid light chain amyloidosis.
• Active central nervous system (CNS) MM.
• Pregnancy or breastfeeding.
• Chemotherapy ≤ 4 week, radiation and immunotherapy ≤ 4 weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1.
• Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 Day 1
• Life expectancy of < 4 months.
• Major surgery within four weeks prior to Cycle 1 Day 1.
• Active, unstable cardiovascular function:

• Symptomatic ischemia, or
• Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
• Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or
• Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1.
• Prior exposure to a SINE compound, including ATG-010.