HCMT/MM2401: Ph2 Study of Selinexor + Bispecific Antibody for RRMM

Prior treatment

• 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.
• 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 who are unable or unwilling to take supportive medications such as anti-nausea and anti anorexia agents as recommended by the NCCN CPGO for antiemesis and anorexia/cachexia (palliative care)
• Patients with contraindication to any of the required concomitant drugs or supportive treatments

Other illness

• 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.

Lab values

• 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

Other

• Females who are pregnant or breastfeeding females.
• 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 unwilling or unable to comply with the protocol

• 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 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 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
• Adequate hepatic function measured on labs collected within 28 days of C1D1:
  • Total bilirubin \<1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \<3 × ULN), and
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to \<2.5 × ULN.
• Adequate renal function measured on labs collected within 28 days of C1D1. Adequacy will be determined by creatinine clearance with values of ≥ 15 mL/min meeting inclusion criteria. Creatinine Clearance will be calculated using the Cockcroft and Gault formula \[(140 - Age) x Mass (kg)/ (72 x creatinine mg/dL); multiply by 0.85 if female\] (Cockcroft 1976).
• Adequate hematopoietic function measured on labs collected within 7 days of C1D1:
  • Absolute neutrophil count ≥1500/mm3
  • Hemoglobin ≥8.5 g/dL
  • Platelet count ≥100,000/mm3 (patients for whom \<50% of bone marrow nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of bone marrow nucleated cells are plasma cells)
  • Note 1: 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.
  • Note 2: 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. Highly effective methods of contraception are listed in Section 9.3.1.
• 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.