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

Karyopharm Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Moderate Thrombocytopenia; Myelofibrosis

Treatments: Drug: Selinexor 40 mg; Drug: Selinexor 60 mg; Drug: Ruxolitinib; Drug: Pacritinib; Drug: Momelotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05980806

XPORT-MF-044

Details and patient eligibility

About

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.

Enrollment: 118 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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118 participants in 4 patient groups

Selinexor 60 mg (Arm 1)

Experimental group

Description:

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.

Treatment:

Drug: Momelotinib

Drug: Pacritinib

Drug: Ruxolitinib

Drug: Selinexor 60 mg

Selinexor 40 mg (Arm 2)

Experimental group

Description:

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.

Treatment:

Drug: Momelotinib

Drug: Pacritinib

Drug: Ruxolitinib

Drug: Selinexor 40 mg

Selinexor 60 mg (Optional Expansion Arm)

Experimental group

Description:

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 \[g/dL\]).

Treatment:

Drug: Momelotinib

Drug: Pacritinib

Drug: Ruxolitinib

Drug: Selinexor 60 mg

Selinexor 40 mg (Optional Expansion Arm)

Experimental group

Description:

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).

Treatment:

Drug: Momelotinib

Drug: Pacritinib

Drug: Ruxolitinib

Drug: Selinexor 40 mg