Selinexor (XPO1) Yields 13.6-mo mPFS in Thymoma, 7.8-mo in Thymic Carcinoma (Phase II)

Selinexor, an oral exportin-1 (XPO1/CRM1) inhibitor, was tested in two coordinated single-arm Phase II trials (US/EU) in pretreated advanced thymic epithelial tumors (n=31; median 2 prior lines). Dosed twice weekly for 3 weeks on/1 week off (starting 60 mg then reduced to 40 mg for tolerability), efficacy included 1 CR in TC (ORR 6.7%) and 2 PRs in thymoma (ORR 12.5%); stable disease occurred in 69% (T) and 80% (TC). Median PFS was 13.6 mo in thymoma (OS not reached) and 7.8 mo in TC (mOS 15.5 mo); toxicity was dominated by cytopenias and constitutional AEs (grade≥3: anemia 16.1%, thrombocytopenia 12.9%, asthenia 12.9%), with dose reductions/interruptions in 64.5% each. Context: in TC, active comparators report higher response rates—lenvatinib ORR 38% with mPFS ~9–10 mo, sunitinib ORR 26% with mPFS ~7 mo, and pembrolizumab ORR 22% with mPFS ~6 mo—suggesting selinexor’s disease control does not exceed established options on response and may trade off for tolerability.