Phase II study to evaluate the efficacy and safety of oral selinexor in patients with recurrent gliomas; The BOSTON study is evaluating once-weekly XPOVIO (selinexor) in combination with once-weekly Velcade (bortezomib) and low-dose dexamethasone (SVd) compared to standard twice-weekly Velcade plus low-dose dexamethasone (Vd) in patients with multiple myeloma who have received one to three prior lines of therapy.

 

Abstract No : 2565

Abstract Type : Poster Discussion Session

Indication : Glioblastoma Multiforme

Intervention : Selinexor

Company : KaryoPharm

Technology : Selective Inhibitor of Nuclear Export (SINE)

 

Results:

Two mutated genes were associated with longer survival in selinexor treated pts: DOCK8 (n = 7; progression free survival [PFS], P = 0.013, hazard ratio [HR] = 3.75 [1.32- 10.62]; overall survival, P = 0.009, HR = 15.39 [2.00-118.34]) and PDX1 (n = 5, PFS, P = 0.014, HR = 4.468 [1.361-14.670]). Other commonly mutated genes in glioma, including IDH1 (n = 9) were observed but not associated with survival. Protein activities inferred from RNA sequencing data were also correlated with response to selinexor. In a machine learning model, ZC3H12A (also called MCPIP1), a negative regulator of inflammation; RAB43, a member of the RAS family that binds GTP and regulates vesicle trafficking, and SOCS3, a suppressor of cytokine signaling that can antagonize JAK/ STAT signaling and repress innate immunity, predicted clinical benefit from selinexor (area under the ROC curve from leave one out cross validation = 0.89, permutation test P , 0.04).

 

Conclusion:

DOCK8 and PDX1 mutations were favorable prognostic factors in selinexor treated pts. Activity of three proteins (ZC3H12A, RAB43, and SOCS3) predicted clinical benefit from selinexor. Further studies with more pts are required to validate our findings.

 

Commentary:

Mutations in DOCK8, EP 400, and PDX1 were favorable prognostic biomarkers associated with longer survival in selinexor treated patients. Activity of three proteins (ZC3H12A, RAB43, and SOCS3) predicted clinical benefit from selinexor. Further studies with more pts are required to validate our findings.

 

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