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

NCT06822972 | Recruiting Phase 2 FDA Drug

• 1 other identifier: Pro00115964
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to determine the safety of single agent Selinexor given with commercial bispecific antibody therapy in patients with Relapsed/Refractory Multiple Myeloma (RRMM) and to determine the MRD negativity rate at 10-5 at 12 months post bispecific antibody therapy. The investigators will enroll 27 patients with RRMM who are receiving commercial bispecific antibody therapy. Patients will be on treatment for 12 months or until disease progression, and will be followed for 24 months. Study assessments include completing a drug diary, having a safety check in call, and have history, clinical assessments, and labs taken. Twenty-seven patients will provide 80% power in a one-sample chi square test for a proportion assuming that the rate of negative MRD at 10-5 at 12 months post bispecific antibody therapy is 25% in historical control and 50% in the SEL+bispecific antibody experimental treatment group, under a one-sided 5% significance level.

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma, Refractory

Outcome Measures

Primary Outcomes (2)

• Safety of selinexor given with commercial bispecific antibody as measured by severity of adverse events

  Adverse events are defined using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  up to 13 months

• Minimal residual disease (MRD) negativity rate post bispecific antibody therapy

  MRD at 10\^-5 will be performed by Clonoseq (Adaptive Biotechnologies) or, if Clonoseq could not be performed due to inability to obtain/identify original plasma cell clone, by Duke institutional flow cytometry-based MRD assay.

  up to 12 months

Secondary Outcomes (9)

• Overall response rate (ORR)

  up to 13 months

• Complete remission (CR) rate

  up to 13 months

• Very good partial response (VGPR) rate

  up to 13 months

• Partial response (PR) rate

  up to 13 months

• Progression free survival (PFS)

  up to 13 months

Study Arms (1)

Selinexor + bispecific antibody

EXPERIMENTAL

Drug: Selinexor 40 mg

Interventions

Selinexor 40 mg DRUG

Patients will receive 40mg of oral SEL, weekly, beginning after they have completed step-up dosing and are 5 (± 2) days out from administration of the first full treatment dose of bispecific antibody therapy for 12 months or until disease progression.

Selinexor + bispecific antibody

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 hematopoietic function measured on labs collected within 7 days of C1D1:

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27705, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Yubin Kang, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lauren Hill

CONTACT

9196682369; lauren.hill@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2025
• First Posted: February 12, 2025
• Study Start: August 22, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)