A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia (SENTRY-2)

A Phase 2 Study to Evaluate the Efficacy and Safety of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia

The main purpose of this study with corresponding optional expansion is to evaluate the efficacy of selinexor in JAKi-naïve participants with myelofibrosis (MF) and moderate thrombocytopenia based on spleen volume reduction (SVR). Additional efficacy and safety parameters will also be assessed during the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Myelofibrosis; Moderate Thrombocytopenia
• Intervention / Treatment: Drug: Selinexor 60 mg; Drug: Ruxolitinib; Drug: Pacritinib; Drug: Momelotinib; Drug: Selinexor 40 mg

• Study Type: Interventional
• Enrollment (Estimated): 118
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Karyopharm Medical Information; Phone Number: (888) 209-9326; Email: clinicaltrials@karyopharm.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• A diagnosis of MF or post-ET or post-PV MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report.
• Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than equal to (>=) 450 cubic square centimeter (cm^3) by MRI or CT scan (results from MRI or CT imaging performed within 28 days prior to screening are acceptable).
• Participants with DIPSS risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk.
• ECOG Performance Status less than or equal to (<=) 2.
• Platelet count of 50 to less than (<) 100 x 10^9/L without platelet transfusion within 7 days prior to the first dose of selinexor.
• Absolute neutrophil count (ANC) >=1.0 × 10^9/L without need for growth factors within 7 days prior to the first dose of selinexor.
• Adequate liver function as defined by the following: aspartate transaminase (AST) and alanine aminotransferase (ALT) <= 2.5 × upper limit normal (ULN) and serum total bilirubin <= 3×ULN.
• Calculated creatinine clearance (CrCl) greater than (>) 15 milliliter per minute (mL/min) based on the Cockcroft and Gault formula.
• Active symptoms of MF as determined by presence of at least 2 symptoms with a score >= 3 or total score of >= 10 at screening using the MFSAF V4.0.
• Participants must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study.
• Participants currently not a candidate for stem cell transplantation.
• Participants must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50).

Key Exclusion Criteria:

• More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase).
• Previous treatment with JAK inhibitors for MF.
• Previous treatment with selinexor or other XPO1 inhibitors.
• Female participants who are pregnant or lactating.
• Prior splenectomy, or splenic radiation within 6 months prior to C1D1.
• History of myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG), cerebrovascular accident (stroke or transient ischemic attack [TIA]), ventricular arrhythmias, congestive heart failure New York Heart Association (NYHA) class > 2 within 6 months of C1D1.
• Participants unable to tolerate two forms of antiemetics prior to each dose for the first two cycles.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selinexor 60 mg (Arm 1); Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first and followed by optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values.	Drug: Selinexor 60 mg; Participants will receive selinexor 60 mg oral tablets QW.; Other Names: KPT-330; Drug: Ruxolitinib; Participants will receive ruxolitinib 5 mg or 10 mg twice daily.; Other Names: JAKAFI; Drug: Pacritinib; Participants will receive pacritinib 200 mg twice daily.; Other Names: VONJO; Drug: Momelotinib; Participants will receive momelotinib 200 mg once daily.; Other Names: OJJAARA
Experimental: Selinexor 40 mg (Arm 2); Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first and followed by optional add-on medication dosing may be initiated based on SVR values.	Drug: Ruxolitinib; Participants will receive ruxolitinib 5 mg or 10 mg twice daily.; Other Names: JAKAFI; Drug: Pacritinib; Participants will receive pacritinib 200 mg twice daily.; Other Names: VONJO; Drug: Momelotinib; Participants will receive momelotinib 200 mg once daily.; Other Names: OJJAARA; Drug: Selinexor 40 mg; Participants will receive selinexor 40 mg oral tablets QW.; Other Names: KPT-330
Experimental: Selinexor 60 mg (Optional Expansion Arm); Participants will receive selinexor 60 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. Optional add-on medication (ruxolitinib [5 mg or 10 mg twice daily], pacritinib [200 mg twice daily], or momelotinib [200 mg once daily]) may be initiated for participants whose SVR is less than (<) 10% at Week 12 or <35% at Week 24 based on the participants platelet count values (i.e., ruxolitinib if platelets greater than or equal to [>=] 50 x 10^9/L, pacritinib if platelets <50 x 10^9/L, momelotinib if platelets is >=50 x 10^9/L and hemoglobin level is < 10 gram per deciliter [g/dL]).	Drug: Selinexor 60 mg; Participants will receive selinexor 60 mg oral tablets QW.; Other Names: KPT-330; Drug: Ruxolitinib; Participants will receive ruxolitinib 5 mg or 10 mg twice daily.; Other Names: JAKAFI; Drug: Pacritinib; Participants will receive pacritinib 200 mg twice daily.; Other Names: VONJO; Drug: Momelotinib; Participants will receive momelotinib 200 mg once daily.; Other Names: OJJAARA
Experimental: Selinexor 40 mg (Optional Expansion Arm); Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. Optional add-on medication (ruxolitinib [5 mg or 10 mg twice daily], pacritinib [200 mg twice daily], or momelotinib [200 mg once daily]) may be initiated for participants whose SVR is <10% at Week 12 or <35% at Week 24 based on the participants platelet count values (i.e., ruxolitinib if platelets >= 50 x 10^9/L, pacritinib if platelets <50 x 10^9/L, momelotinib if platelets is >=50 x 10^9/L and hemoglobin level is < 10 g/dL).	Drug: Ruxolitinib; Participants will receive ruxolitinib 5 mg or 10 mg twice daily.; Other Names: JAKAFI; Drug: Pacritinib; Participants will receive pacritinib 200 mg twice daily.; Other Names: VONJO; Drug: Momelotinib; Participants will receive momelotinib 200 mg once daily.; Other Names: OJJAARA; Drug: Selinexor 40 mg; Participants will receive selinexor 40 mg oral tablets QW.; Other Names: KPT-330

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants with Spleen Volume Reduction 35 (SVR35) at Week 24.	Measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Scan	At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-emergent Adverse Events (TEAEs), Severity of TEAEs, Treatment Related Adverse Events (TRAEs) and Serious Adverse Events (SAEs)		From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)
Overall Survival (OS)		From date of randomization to the date of death due to any cause or EoS (assessed at approximately 48 months)
Duration of Receptor Occupancy or Exportin 1 (XPO1) mRNA Induction		From Baseline up to EoS (approximately 48 months)
Proportion of Participants with Anemia Response at Week 24 as per the International Working Group Myeloproliferative Neoplasms Research and Treatment and European Leukemia Network (IWG-MRT and ELN) Criteria		At Week 24
Overall Response Rate (ORR) as per IWG MRT and ELN Criteria		From Cycle 1 Day 1 (28-day cycle) up to EoS (approximately 48 months)
SVR35 Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)		From Baseline up to EoS (approximately 48 months)
TSS50 Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)		From Baseline up to EoS (approximately 48 months)
Anemia Response in Pre-specified MF Participant Subgroups (Including by Gender, Age, and Geographic Region)		From Baseline up to EoS (approximately 48 months)
SVR35 Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only		At Week 24
TSS50 Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only		At Week 24
Anemia Response in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only		At Week 24
Number of Participants with TEAEs, Severity of TEAEs, TRAEs and SAEs in Participants who Receive as add-on Treatments (Ruxolitinib or Pacritinib or Momelotinib) to Selinexor and Single-agent Selinexor Only		From start of drug administration up to 30 days after the last dose of study treatment (approximately 48 months)
Area Under the Concentration-time Curve (AUC) of Selinexor		Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
Maximum Plasma Concentration (Cmax) of Selinexor		Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
Time at Which Cmax is Achieved (Tmax) of Selinexor		Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 15 and 2 hours post-dose on Cycle 2 Day 15 (28-day cycle)
Proportion of Participants with Post-treatment Changes in Bone Marrow		From Baseline up to EoS (approximately 48 months)
Proportion of Participants with Total Symptom Score 50 (TSS50) at Week 24.	Measured by the Myelofibrosis Symptom Assessment Form (MFSAF) V4.0. A higher Total Symptom Score (TSS) indicates a higher disease burden and thus a worse outcome.	At Week 24
Proportion of Participants with SVR35 at Any Time Point.	Measured by MRI or CT Scan.	From Baseline to EoS (approximately 48 months)
Proportion of Participants with TSS50 at Any Time.	Measured by the MFSAF V4.0. A higher Total Symptom Score (TSS) indicates a higher disease burden and thus a worse outcome.	From Baseline to EoS (approximately 48 months)

Collaborators and Investigators

• Sponsor: Karyopharm Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Ruxolitinib; Myelofibrosis; JAK2; KPT-330; Thrombocytopenia; Selinexor; Pacritinib; Momelotinib; Total Symptom Score; Spleen Volume Reduction; TSS50; SVR35; Myelofibrosis Symptom Assessment Form
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Blood Platelet Disorders; Cytopenia; Primary Myelofibrosis; Thrombocytopenia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
• Other Study ID Numbers: XPORT-MF-044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No