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.

P2, N=43, Recruiting, Beijing Tongren Hospital

P3, N=263, Completed, Karyopharm Therapeutics Inc | Active, not recruiting --> Completed

In this preclinical study, we demonstrate that the MI ziftomenib, in combination with the XPO1 inhibitor selinexor, synergistically inhibited the growth of multiple KMT2A- r and NPM1 -m AML cell lines (CI<1). In vivo , combination therapy improved survival in both MV4;11 and OCI-AML3 cell line and primary patient-derived KMT2A - r and NPM1 -m AML xenograft models in NSG mice, effective even at reduced drug doses. These preclinical findings demonstrate that simultaneous inhibition of the menin-KMT2A interaction and XPO1 can be a more effective translational strategy for treating KMT2A- r and NPM1 -m AML than MI monotherapy to deepen responses and delay/prevent relapses.

P=N/A, N=127, Recruiting, Shanxi Bethune Hospital

In vivo PET imaging in MM xenograft models demonstrated that &lsqb;68Ga]Ga-NOTA-selinexor achieved superior imaging contrast and a significantly higher T/M ratio (∼4.4) compared to previously reported &lsqb;18F]selinexor (∼2.1). Taken together, these findings suggest that &lsqb;68Ga]Ga-NOTA-selinexor serves as a valuable PET tracer for noninvasively evaluating XPO1 expression in vivo, highlighting its potential for both precise diagnosis and treatment assessment in MM.

P1/2, N=33, Active, not recruiting, Suzhou Junjing BioSciences Co., Ltd. | Recruiting --> Active, not recruiting | N=49 --> 33

We previously identified MDM2 as a therapeutic vulnerability in RTs and showed that treatment with the MDM2 inhibitor idasanutlin (IDA) increased survival in mice bearing MRT xenografts...We hypothesized that combining IDA with selinexor (SEL), a CNS penetrant XPO1 inhibitor, would potentiate p53-mediated activation and increase therapeutic response in vivo...The BCL-2 family of proteins was identified as key modulators of intrinsic and acquired resistance. Combining MDM2 inhibitors and XPO1 inhibitors is a promising therapeutic strategy for treating children with ATRT.

The combination strategy provides a novel potential approach for improving the therapeutic efficacy of sorafenib and overcoming both intrinsic and acquired sorafenib resistance in HCC. The main limitations of this study are the lack of RT-PCR verification and further detection of downstream apoptotic effector molecules, which need to be explored in future research.

P1, N=20, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting