On November 3, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that two abstracts detailing new selinexor data have been selected for poster presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place December 10-13, 2022 (Press release, Karyopharm, NOV 3, 2022, View Source [SID1234622935]). The presentations include results from the Phase 1 open-label, dose-escalation study of selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis (MF) and data from a subset analysis of the STOMP study in patients with triple-class refractory MM.
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Results from Phase 1 Study Evaluating Selinexor in Combination with Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis
The data included in the abstract for ASH (Free ASH Whitepaper) 2022 were based on the Phase 1 portion of the Phase 1/2 study evaluating the safety and preliminary efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389). As of July 2022, 19 patients had been assigned to either selinexor 40 mg or 60 mg, in combination with ruxolitinib 15/20 mg BID.
Seventy-nine percent of efficacy evaluable patients (11 out of 14) demonstrated ≥35% reduction in spleen volume (SVR35) at week 12 and 86% (6 out of 7) achieved SVR35 at week 24. Thirteen patients who had received at least 12 weeks of treatment experienced rapid improvements in their symptom scores, with 69% (9 out of 13) of efficacy evaluable patients having ≥50% reduction (TSS50). Eleven out of 17 transfusion-independent patients (65%) who had at least eight weeks of treatment maintained stable hemoglobin (± 2g/dL) or improved hemoglobin level (>2g/dL increase) at last follow up.
"We remain very encouraged by the notable activity across three clinically meaningful efficacy endpoints relevant to patients with MF including spleen volume reduction, improvement in symptom score and hemoglobin stabilization," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "We look forward to observing how the efficacy and safety evolve across the two doses and engaging with the FDA on the registrational portion of this trial."
The data observed across both the 40mg and 60mg assigned groups demonstrate a generally manageable side effect profile with no dose-limiting toxicities observed at either dose level in the Phase 1a dose escalation portion of the study. The most common adverse events (AEs) were nausea (58%), anemia (42%) and vomiting (42%), the majority of which were grades 1-2. The most common reported grade 3-4 treatment-emergent AEs were thrombocytopenia (26%) and anemia (21%), both of which were reversible. Updated data from this study, including results from additional patients, will be presented at the ASH (Free ASH Whitepaper) meeting in December 2022.
"The addition of novel agents to JAK inhibitors is an intriguing approach to improve depth and duration of responses compared to JAK inhibition alone," said Dr. Haris Ali, City of Hope Comprehensive Cancer Center. "The introduction of a novel mechanism of SINE inhibition, in combination with a JAK inhibitor, may provide patients an upfront treatment option that could improve clinical outcomes with a manageable safety profile."
Details for the ASH (Free ASH Whitepaper) 2022 abstracts are as follows:
Poster Presentations
Title: A Phase 1, Open-Label, Dose-Escalation Study of Selinexor Plus Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis
Presenter: Dr. Ali, City of Hope Comprehensive Cancer Center
Abstract #: 1734
Session Type: Poster Presentation
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Date and Time: Saturday, December 10, 2022, 5:30 PM – 7:30 PM CT
Title: Once Weekly Selinexor, Carfilzomib and Dexamethasone (XKd) in Triple Class Refractory Multiple Myeloma
Presenter: Dr. Schiller, David Geffen School of Medicine at UCLA
Abstract #: 4516
Session Type: Poster Presentation
Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster III
Date and Time: Monday, December 12, 2022, 6:00 PM – 8:00 PM CT
Online Publication
Title: Real-World Safety and Effectiveness of Selinexor-Based Regimens in Patients with Relapsed or Refractory Multiple Myeloma and Dialysis-Dependent Renal Impairment
Presenter: Dr. Niblock, Karyopharm Therapeutics
Abstract #: 5773
Session Type: Online publication
Date and Time: Available in the November supplemental issue of Blood
About XPOVIO (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm’s partners, Antengene, Menarini, Neopharm and FORUS in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada.
Please refer to the local Prescribing Information for full details.
Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.
For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
Email: [email protected]
SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
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