Karyopharm Presents Updated Exploratory Subgroup Analyses from SIENDO Study in Patients with Advanced or Recurrent TP53 Wild-Type Endometrial Cancer During 2024 ASCO Plenary Series: Rapid Abstract Updates
Long-Term Follow-Up Data Signal Promising Progression-Free Survival (PFS) for Selinexor in the Maintenance Setting with Median PFS of 28.4 Months in the TP53 Wild-Type and 39.5 Months in the Proficient Mismatched Repair Status (pMMR) TP53 Wild-Type Exploratory Subgroups
Q-TWiST, an Important Metric Assessing Both Quality and Quantity of Clinical Benefit, Suggests Improvement with Selinexor versus Placebo, which is Critical in the Maintenance Setting
Company Highlights Additional Presentations in Endometrial Cancer and Myelofibrosis at ASCO 2024
The primary analysis of the Phase 3 SIENDO study of selinexor maintenance therapy in advanced or recurrent endometrial cancer showed improvements in median PFS for the intent-to-treat (ITT) population but were not clinically meaningful. However, an exploratory analysis of a pre-specified subgroup of patients with TP53 wild-type endometrial cancer showed a promising efficacy signal.
In the exploratory subgroup analysis, 113 patients with TP53 wild-type advanced/recurrent endometrial cancer were randomized to receive selinexor (n=77) vs placebo (n=36) as maintenance therapy after 1L platinum-based chemotherapy. As of the
The updated analyses also highlighted findings from a quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) used to assess quality and toxicity-adjusted PFS. The findings showed the restricted mean Q-TWiST for selinexor to be 26 months compared to 15 months for placebo, resulting in a difference of nearly 11 months.
"The approximately 40 months median PFS observed with selinexor in patients whose tumors are both TP53 wild-type and pMMR, coupled with the robust QTWiST analysis, suggests that selinexor may be an optimal maintenance therapy in endometrial cancer," said
No new safety signals were identified as of the data cut-off date of
"It is exciting to see the emerging data around progression free survival, as well as an encouraging trend in overall survival and the Q-TWiST metric in the TP53wild-type subgroup analysis from the SIENDO study," said
A copy of the presentation from the "ASCO Plenary Series: Rapid Abstract Updates" special session can be accessed under "Publications and Presentations" in the Investor section of the Company's website, https://investors.karyopharm.com/publications-and-presentations.
Selinexor is being evaluated in a global, Phase 3, randomized, double-blind study, EC-042 (XPORT-EC-042; NCT05611931), as a maintenance therapy following systemic therapy in patients with TP53wild-type advanced or recurrent endometrial cancer. Karyopharm expects to report data from this trial in the first half of 2025.
The following Karyopharm abstracts will also be presented at ASCO:
Abstract Title |
Presentation Type |
Abstract # |
Session Date/Time |
Endometrial Cancer |
|||
Phase 3 Dose Selection for Selinexor in TP53wt Endometrial Cancer Based on Exposure-Response Analysis |
Poster |
5594 |
|
Myelofibrosis |
|||
Phase 3 Randomized Double-Blind Study Evaluating Selinexor, an XPO1 inhibitor, Plus Ruxolitinib in Jaki-Naïve Myelofibrosis |
Poster |
TPS6594 |
|
Phase 2 Study Evaluating Selinexor Monotherapy in Patients with Jaki-Naïve Myelofibrosis and Moderate Thrombocytopenia |
Poster |
TPS6593 |
|
About the EC-042 Study
EC-042 (XPORT-EC-042; NCT05611931) is a global, Phase 3, randomized, double-blind study evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer.
About the SIENDO Study
Karyopharm's evaluation of selinexor to treat patients with TP53 wild-type advanced or recurrent endometrial cancer is supported by data from an exploratory subgroup analysis from its ongoing SIENDO Study, a European Network of Gynaecological Oncological Trial Groups (ENGOT)-led trial in collaboration with the
About Endometrial Cancer
Endometrial cancer is the most common cancer of the female reproductive organs in the
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 approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the
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: medicalinformation@karyopharm.com
SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions
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Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
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Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
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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.
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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.
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Serious Infection: Monitor for infection and treat promptly.
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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.
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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 theBOSTON 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.
Use In Specific Populations
Lactation: Advise not to breastfeed.
For additional product information, including full prescribing information, please visit www.XPOVIO.com.
To report SUSPECTED ADVERSE REACTIONS, contact
About
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor to treat patients with endometrial cancer; and expectations related to the clinical development of selinexor and potential regulatory submissions of selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor and eltanexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the
XPOVIO® and NEXPOVIO® are registered trademarks of
References
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