Xpovio (selinexor)

Despite limited sample size, XPORT-MF-035 provides descriptive data on the safety, tolerability, and biological activity of selinexor monotherapy in previously treated MF, supporting further evaluation in this population. ClinicalTrials.gov identifier: NCT04562870.

Mechanistically, KPT-330 suppressed p65 phosphorylation/nuclear translocation and attenuated MAPK signaling (p38, ERK1/2, and JNK), thereby downregulating osteoclastogenic transcription factors c-Fos and NFATc1. These findings establish XPO1 inhibition as a potential dual-action strategy targeting osteoclast-mediated bone-cartilage crosstalk in OA.

P2, N=15, Not yet recruiting, Zhongshan Hospital (Xiamen), Fudan University

P2, N=27, Recruiting, Duke University | Trial primary completion date: Apr 2026 --> Dec 2026

In patients with JAK inhibitor-naïve myelofibrosis, selinexor plus ruxolitinib met its co-primary endpoint of improved SVR35 but did not meet the AbsTSS co-primary endpoint, compared with placebo plus ruxolitinib. An early OS difference was observed. The safety profile was consistent with known adverse event profiles of the individual agents.

P2, N=20, Completed, The First Affiliated Hospital of Soochow University | Recruiting --> Completed

Selinexor, an exportin 1 inhibitor to impede NPM1MU export from nucleus, enhances FTO degradation and reduces macrophage M2 polarization. This work reveals that FTO-creatine signaling plays an oncogenic role in NPM1MU AML, guiding more effective therapy strategies and clinical benefits for this distinctly leukemic entity.

P3, N=257, Active, not recruiting, Karyopharm Therapeutics Inc | Recruiting --> Active, not recruiting

P1, N=16, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026

P1, N=22, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Nov 2025 | Trial primary completion date: Jun 2026 --> Nov 2025

FASN represents a novel independent prognostic biomarker in DMPM patients undergoing CRS+HIPEC and a promising therapeutic target. Given the limited treatment options for DMPM, combination strategies incorporating FASN inhibitors with selinexor or TEAD-pathway-targeting agents, supported by existing clinical trial data, may offer a rapidly translatable therapeutic approach.

Venetoclax and selinexor retained activity in resistant models, supporting their potential for rational combinations with TK216. These findings demonstrate that multiple, heterogeneous mechanisms drive resistance to ETS inhibition in DLBCL, highlighting therapeutic strategies to overcome it.