Xpovio (selinexor)

P1, N=16, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2025 --> Jun 2026

P1, N=22, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=39 --> 22

Among increasingly personalised strategies, particular promise is shown by HER2-targeted therapies for HER2-positive malignancies (e.g. trastuzumab deruxtecan). Additionally, targeting TP53 wild-type tumours with selinexor, as well as addressing AKT and DNA repair pathways in both uterine carcinomas and sarcomas (i.e. AKT inhibitor and poly(ADP-ribose) polymerase inhibitor combinations), represents key advancements. Furthermore, anti-angiogenic and immune checkpoint inhibitor combinations hold significant promise for future therapeutic strategies.

The data suggest that SLX may decrease cell viability, induce apoptosis, inhibit cell migration and increase DNA damage and cellular stress in male germ cells. Given these effects, SLX should be carefully examined for its potential reproductive toxicity. Further studies are warranted to explore its long-term impact on male fertility.

Covalent selective inhibitors of nuclear export (SINEs), including the cancer drug selinexor, restore proper nuclear localization by blocking XPO1-cargo interaction...ASB8-mediated degradation is also triggered by the endogenous itaconate derivative 4-octyl itaconate, suggesting that synthetic XPO1 inhibitors exploit a native cellular mechanism. This allosteric XPO1 degradation mechanism expands known modes of targeted protein degradation beyond molecular glue degraders and proteolysis-targeting chimeras of CRL4.

P1, N=52, Completed, University of Chicago | Recruiting --> Completed | N=100 --> 52 | Trial completion date: Dec 2026 --> Oct 2025 | Trial primary completion date: Jul 2026 --> Oct 2025

The main determinant of second-line therapy selection includes refractoriness, particularly to lenalidomide and anti-CD38 monoclonal antibodies, followed by cytogenetic risk, relapse aggressiveness, frailty, and patient preferences...Combinations based on belantamab mafadotin, an antibody drug conjugate targeting B cell maturation antigen (BCMA), are currently the leading non CAR-T options in this setting, while exportin-1 inhibitors, such as selinexor, and next-generation proteasome inhibitors offer additional options. Ongoing trials assessing T-cell redirecting bispecific antibodies targeting B cell maturation antigen or GPRC5D may further improve outcomes at first relapse as access and safety profiles evolve. In conclusion, early-relapse multiple myeloma care should be individualized in order to optimize patient outcomes and achieve long-term remissions with acceptable toxicity profile.

P=N/A, N=39, Not yet recruiting, Shanghai General Hospital; Shanghai General Hospital

Furthermore, we found that, like OCI-AML cells, the exportin 1 (XPO1) inhibitors selinexor and eltanexor significantly induced cell cycle arrest and reduced PHGDH expression in OCI-AML3-OR cells. Therefore, treatment with PHGDH inhibitors could be a therapeutic strategy for refractory AML to PI3K/mTOR inhibitors. Relevant clinical trials are warranted.

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

P=N/A, N=0, Available, Karyopharm Therapeutics Inc