Multicenter phase 1 study of gemcitabine plus selinexor in selected advanced sarcomas

Exportin-1 (XPO-1) is related to drug resistance and poor prognosis in solid tumors. Selinexor is an XPO-1 inhibitor with preclinical and clinical activity in sarcomas. A multicenter phase 1 trial in Spain explored the combination of gemcitabine and selinexor for selected advanced sarcomas. Seventeen adult patients received gemcitabine and weekly selinexor in 21-day cycles in a classic 3 + 3 design. The recommended phase 2 dose (primary endpoint) was determined to be gemcitabine 1200 mg/m² at 10 mg/m²/min followed by 60 mg weekly selinexor. The most freqent adverse events were neutropenia (82.4% of patients) and thrombocytopenia (76.5%). The objective response rate was 31.25% and the median overall survival was 39.5 months (95% CI 12.4-67) wit a 36-month overall survival rate of 50.2%. A phase 2 trial is currently exploring this combination in leiomyosarcoma and malignant peripheral nerve sheath tumors.