Xpovio (selinexor)

P1, N=20, Not yet recruiting, Washington University School of Medicine | Trial completion date: Dec 2030 --> Mar 2031 | Initiation date: Dec 2025 --> Mar 2026

Cell lines representing DLBCL subtypes were treated with varying concentrations of the XPO1 inhibitor selinexor (XPO1i), cisplatin (CDDP), and oxaliplatin (OXA), alone or in combination. In OCI-Ly8 and OCI-Ly1 cells, OXA alone inhibited phosphorylation of AKT and mTOR while increasing phosphorylation of JNK, ATM, and p53, and expression of γH2AX; these effects were potentiated by the combination of XPO1i and OXA. XPO1 inhibition enhances platinum-induced cytotoxicity in GCB-DLBCL, supporting clinical evaluation of XPO1i-platinum combinations as salvage therapy.

Isogenic PDX models of TNBC provide a powerful platform to define molecular mechanisms of acquired carboplatin resistance and uncover actionable therapeutic strategies. Our findings reveal multiple adaptive routes to platinum resistance, including restoration of homologous recombination and activation of alternative DNA repair programs. Synergistic interactions between SG and mTOR inhibition offer a promising avenue for overcoming resistance, supporting further clinical investigation of these combinations in TNBC.

P=N/A, N=40, Not yet recruiting, Department of Hematology, Fifth Medical Center of the PLA General Hospital; Fifth Medical Center of the PLA General Hospital

P3, N=390, Recruiting, West China Hospital of Sichuan University/Ruijin Hospital of Shanghai Jiao Tong University School of Medicine; Chengdu Zenitar Biomedical Technology C

P1/2, N=4, Terminated, Mamta Parikh | N=12 --> 4 | Recruiting --> Terminated; Poor accrual.

P2/3, N=28, Recruiting, Beijing Friendship Hospital

P1, N=37, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Feb 2026 --> Sep 2027

Our preclinical data highlighted the potential synergistic efficacy of chidamide and selinexor in targeting HGBL-DHL, providing a rationale for further clinical investigation of this therapeutic combination for the treatment of this refractory disease.

P1, N=11, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2026 --> Jul 2028

A female patient in her late 40s with Stage IVB EGFR L858R lung adenocarcinoma exhibiting high BCL-2 expression was treated with radiotherapy and icotinib...Upon AML relapse, a fast in vivo MiniPDX drug sensitivity assay guided the selection of a salvage combination therapy (Selinexor, Decitabine, and Venetoclax)...This case highlights the complexity of managing these distinct malignancies, where the lung tumor's BCL-2 expression provided a rationale for the AML therapy. Furthermore, the MiniPDX assay proved valuable in guiding personalized therapy for refractory disease, demonstrating the potential of functional precision medicine strategies.

Treatment of MM cells with the selective AURKA inhibitor LY3295668 induced dose-dependent cytotoxicity, caspase-3/7 activation, and cellular senescence. These findings underscore AURKA expression as a prognostic marker in plasma cell disorders and support the therapeutic potential of combining AURKA inhibition with selinexor for bortezomib-resistant MM and PCL. To explore biomarker-driven strategies for optimizing therapeutic outcomes, future studies are warranted.