Karyopharm Therapeutics Inc. · NASDAQ:KPTI
Karyopharm Therapeutics — ESGO 2025
14 slides from Karyopharm Therapeutics's conference presentation, 2025
Slide 1: Longer-term Safety and Efficacy of Selinexor Maintenance Therapy in TP53wt Endometrial Cancer
Longer-term Safety and Efficacy of Selinexor Maintenance Therapy for Patients With TP53wt Advanced or Recurrent Endometrial Cancer: Follow-up Subgroup Analysis of the ENGOT-EN5/GOG-3055/SIENDO Study Giorgio Valabrega1, Ignace Vergote2, Debra Richardson3, Alejandro Pérez-Fidalgo4, Toon Van Gorp2, Jal
Slide 2: Disclosure
Disclosure Giorgio Valabrega, MD, PhD University of Torino, AO Ordine Mauriziano, Torino, Italy Consulting/ Ownership/ Other Honoraria/ Funded Royalties/ Stock Company Name Advisory Equity Employee (please Expenses Research Patent Options Board Position specify) AstraZeneca X X X Merck Sharp & Dohme
Slide 3: Selinexor is a Novel Oral Maintenance Therapy Targeting TP53wt Endometrial Cancer
Selinexor is a Novel Oral Maintenance Therapy Targeting TP53wt Endometrial Cancer • Immune checkpoint inhibitors showed clinically meaningful benefit in patients with dMMR EC, but benefit in those with pMMR tumors was more modest1-6 • dMMR tumors (mPFS, 30-NR mo; mOS, NR)1-5 • pMMR tumors (mPFS, 10-
Slide 4: Selinexor is a Novel Oral Maintenance Therapy Targeting TP53wt Endometrial Cancer
Selinexor is a Novel Oral Maintenance Therapy Targeting TP53wt Endometrial Cancer • XPO1 inhibition by selinexor results in nuclear retention and functional reactivation of tumor suppressor proteins (TSPs), which selectively kill cancer cells and largely spare normal cells1,4,6 • XPO1 inhibition (XP
Slide 5: ENGOT-EN5/GOG-3055/SIENDO: Phase 3 Maintenance Trial Design
ENGOT-EN5/GOG-3055/SIENDO (NCT03555422): A Randomized, Double-Blind, Phase 3 Trial of Maintenance With Selinexor/Placebo After Combination Chemotherapy for Patients With Advanced or Recurrent Endometrial Cancer Primary endpoint2 Selinexor Is a Novel Oral Maintenance Therapy • PFS, per RECIST v1.1 Ta
Slide 6: Patient Demographics and Baseline Characteristics
Patient Demographics and Baseline Characteristics TP53wt* TP53wt* Selinexor Placebo Selinexor Placebo Characteristics n=77 n=36 Characteristics n=77 n=36 Age, years, median (range) 64.0 (40-81) 61.5 (33-74) Disease at time of taxane-platinum combination therapy, n (%) ≥70 years, n (%) 23 (29.9) 8 (2
Slide 7: Long-term mPFS of 28.4 Months in TP53wt Subgroup
Long-term mPFS of 28.4 Months in TP53wt Subgroup 1.00 Selinexor (n=77): 28.4 months (95% CI 13.1-NR) Placebo (n=36): 5.2 months (95% CI 2.0-13.1) HR: 0.44 (95% CI 0.27-0.73); one-sided nominal P-value = 0.0005 Probability of PFS 0.75 PFS calculation begins at randomization of maintenance therapy 0.5
Slide 8: Long-term mPFS in TP53wt/pMMR and TP53wt/dMMR Subgroups
Long-term mPFS of 39.5 Months and 13.1 Months in TP53wt/pMMR and TP53wt/dMMR Subgroups, Respectively TP53wt/pMMR TP53wt/dMMR Selinexor (n=47): 39.5 months (95% CI 19.3-NR) Selinexor (n=20): 13.1 months (95% CI 3.6-NR) Placebo (n=23): 4.9 months (95% CI 2.0-NR) Placebo (n=9): 3.7 months (95% CI 1.9-N
Slide 9: Preliminary Overall Survival
Preliminary Overall Survival Median, months HR Nominal one- Median follow-up % with events Overall maturity (95% CI) (95% CI) sided P-value (months) TP53wt Selinexor (n=77) 24.7% NR (45.4-NR) 0.65 29.2% 0.11 36.8 Placebo (n=36) 38.9% NR (35.2-NR) (0.32-1.29) TP53wt/pMMR Selinexor (n=47) 25.5% NR (45
Slide 10: Treatment-emergent Adverse Events
Treatment-emergent Adverse Events Selinexor (n=76*) Placebo (n=35*) Nausea 90% 13% 40% Vomiting 60% 3% 3% 14% Diarrhea 45% 4% 37% Constipation 33% 6% 40% Asthenia 36% 5% 26% Fatigue 36% 8% 20% Thrombocytopenia 42% 10% 3% Decreased appetite 36% 3% Neutropenia 34% 20% 6% Any grade in ≥20% of patients
Slide 11: Exploratory Q-TWiST Analysis of TP53wt/pMMR Subgroup
Exploratory Q-TWiST Analysis of TP53wt/pMMR Subgroup • In the TP53wt group, the clinically meaningful improvement in PFS was maintained while adjusting for quality of life and toxicity, with a difference of 10.63 months • Additionally, a clinically meaningful improvement in PFS was observed in the T
Slide 12: Results Support the Ongoing Phase 3 XPORT-EC-042 Trial
These Results Further Support the Ongoing Phase 3 ENGOT-EN20/GOG-3083/XPORT-EC-042 Trial of Selinexor 60 mg QW as Maintenance Therapy in Patients With Advanced or Recurrent TP53wt EC • A marked PFS benefit was observed with selinexor maintenance therapy in the novel TP53wt/pMMR subgroup (mPFS 39.5 m
Slide 13: ENGOT-EN20/GOG-3083/XPORT-EC-042 Selinexor Maintenance Therapy Trial
ENGOT-EN20/GOG-3083/XPORT-EC-042 (NCT05611931) Selinexor Maintenance Therapy After Systemic Therapy for Patients With Advanced or Recurrent P53wt Endometrial Carcinoma Study is ongoing and actively enrolling Primary endpoint • PFS assessed by investigator Planned enrollment Key secondary endpoint (N
Slide 14: Acknowledgments
Acknowledgments We thank participating patients and their families, all investigators, and academic study groups for participating in the SIENDO trial LogoMG BGOG GOG GEICO CEEGOG MITO ISGO NOGGO USOC HeCOG China Canada USA Vergote Randall Perez-Fidalgo Cibula Valabrega Helpman Sehouli Tibayan Fount