P2, N=47, Not yet recruiting, Sun Yat-sen University

P2, N=244, Active, not recruiting, Karyopharm Therapeutics Inc | Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> Dec 2026 | Trial primary completion date: Apr 2027 --> Dec 2026

P2/3, N=501, Active, not recruiting, Karyopharm Therapeutics Inc | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P1/2, N=300, Active, not recruiting, Karyopharm Therapeutics Inc | Recruiting --> Active, not recruiting

Our findings demonstrate that ZR interacting proteins constitute therapeutic leads, and that XPO1 is critical for titrating 'goldilocks' levels of ZR nuclear expression. We identify a novel combination therapy of Selinexor, Gemcitabine, and Ribociclib that may be immediately translated into clinical trials for EPN patients that are currently without targeted treatments.

XPO1 hyperactivation rewires nucleocytoplasmic transport and sustains leukaemogenic programs in genetically defined acute myeloid leukaemia (AML) subsets. Selective XPO1 inhibitors (selinexor, eltanexor) show preferential activity in NPM1-mutated, DEK::NUP214-positive and SF3B1-mutated myeloid neoplasms. Combination strategies with hypomethylating agents, BCL-2 inhibitors and other targeted therapies enhance depth and durability of responses but are limited by toxicity. Future clinical trials should focus on molecularly selected populations, biomarker-guided dosing and translational endpoints such as measurable residual disease (MRD) and clonal dynamics.

P2, N=34, Not yet recruiting, Beijing Tongren Hospital

Drug interaction analyses assessed the combined effect of Selinexor and Mitoxantrone. E2F7-mediated HR inhibition is a key mechanism underlying Selinexor activity in AML. The XPO1-E2F7-HR axis represents a potential therapeutic vulnerability, supporting the rational combination of Selinexor with DNA-damaging agents to improve AML treatment outcomes.

P1/2, N=37, Recruiting, Samsung Medical Center | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2026 --> Dec 2028

Our study found that inhibition of XPO1 is a promising modality in the treatment of MDS, especially when combined with Venetoclax, which could be a potential target for MDS therapy.

P2, N=129, Active, not recruiting, Canadian Cancer Trials Group | Trial primary completion date: Mar 2026 --> Jun 2026

Furthermore, we identify a synergistic antitumor effect between KPT-330 and translation inhibitors, including everolimus and homoharringtonine. Notably, the disruptive impact of KPT-330 on CRC homeostasis extends to other cancer cell lineages, underscoring its broad mechanistic relevance. Collectively, our findings elucidate a novel mechanism through which KPT-330 destabilizes CRC via translational dysregulation and highlight its potential therapeutic utility in combination regimens for DDLPS.