Selinexor with Bispecific Antibody Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• Age ≥ 18 years old at the time of informed consent
• Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• A diagnosis of symptomatic multiple myeloma, with relapsed or refractory disease. Patients must have received at least 4 prior lines of therapy. Prior lines of therapy must include a proteasome inhibitor, an immunomodulatory agent, and an CD38 monoclonal antibody, and may include treatment with B-cell maturation antigen (BCMA) antibody conjugates or BCMA directed chimeric antigen receptor (CAR) T cell therapy
• All patients must meet criteria for and will receive teclistamab, elranatamab or talquetamab, as per approved label dosing
• Patients who have had CRS/ICANS from bispecific antibody must have complete resolution of CRS/ICANS before initiation of selinexor (SEL)
• Measurable disease as defined by at least one of the following: * Serum monoclonal (M) protein ≥ 1.0 g/dl by protein electrophoresis * >200 mg of M protein in the urine on 24 hour electrophoresis * Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio * Measurable plasmacytoma
• Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert’s syndrome who must have a total bilirubin of < 3 × ULN) (measured on labs collected within 28 days of cycle [C] 1 day [D] 1).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to < 2.5 × ULN (measured on labs collected within 28 days of C1D1)
• Creatinine clearance with values of ≥ 15 mL/min (measured on labs collected within 28 days of C1D1). Creatinine Clearance will be calculated using the Cockcroft and Gault formula
• Absolute neutrophil count ≥ 1500/mm^3 (measured on labs collected within 7 days of C1D1) * Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag, romiplostim, interleukin-11) are eligible. * Patients must have at least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive red blood cell (RBC) and/or platelet transfusions as clinically indicated per institutional guidelines during the study
• Hemoglobin ≥ 8.5 g/dL (measured on labs collected within 7 days of C1D1) * Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag, romiplostim, interleukin-11) are eligible. * Patients must have at least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study
• Platelet count ≥ 100,000/mm^3 (patients for whom < 50% of bone marrow nucleated cells are plasma cells) or ≥ 50,000/mm^3 (patients for whom ≥ 50% of bone marrow nucleated cells are plasma cells) (measured on labs collected within 7 days of C1D1) * Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag, romiplostim, interleukin-11) are eligible. * Patients must have at least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study
• Patients who are able to become pregnant must have a negative serum pregnancy test at screening
• All patients who could become pregnant or could father a child must use highly effective methods of contraception throughout the study and for 5 months following the last dose of study treatment
• Female patients must agree not to donate egg during the study treatment period and/or up to 90 days after the last dose of Selinexor. Male patients must agree not to donate sperm during the study treatment period and/or up to 90 days after the last dose of selinexor

Exclusion Criteria

• Patients who have received and were refractory to selinexor or another specific inhibitor of nuclear exporter (SINE) compound previously. * Note: Patients who were exposed to selinexor or another SINE compound but were not refractory are eligible
• Patients with any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection) that is likely to interfere with study procedures
• Patients with any uncontrolled active infection requiring medical or surgical management within 1 week prior to cycle 1 day 1 (C1D1). * Note: Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are eligible
• Females who are pregnant or breastfeeding females
• Patients with active, unstable cardiovascular function, as indicated by the presence of any of the following: * Symptomatic ischemia * Uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on anti-arrhythmics); ** note: patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block are eligible * Congestive heart failure of New York Heart Association Class ≥ 3 * Known left ventricular ejection fraction < 40% * Myocardial infarction within 3 months prior to C1D1
• Patients with well controlled chronic viral hepatitis and/or Human Immunodeficiency Virus can be considered for the study if they meet any of the following conditions: * Patients with active hepatitis B virus (Hep B) who have been on antiviral therapy for hepatitis B for > 8 weeks and whose viral load is < 100 IU/ml prior to first dose of trial treatment * Patients with treated or untreated hepatitis C virus (HCV) and successfully treated and “cured” HCV * Patients with Human Immunodeficiency Virus (HIV) who have CD4+ T-cell counts ≥ 350 cells/µL and no history of AIDS-defining opportunistic infections in the last year
• Patients who still have any grade of CRS/ICANS at 5 (± 2) days of administration of the first full treatment dose of bispecific antibody treatment will be excluded
• Patients with any active gastrointestinal dysfunction interfering with their ability to swallow tablets or any active gastrointestinal dysfunction that could interfere with absorption of study treatment
• Patients who are unable or unwilling to take supportive medications such as anti-nausea and anti anorexia agents as recommended by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (CPGO) for antiemesis and anorexia/cachexia (palliative care)
• Patients who have any psychiatric, medical, or other condition that, in the opinion of the investigator, could interfere with treatment, compliance, or the ability to give informed consent
• Patients with contraindication to any of the required concomitant drugs or supportive treatments
• Patients unwilling or unable to comply with the protocol