A Phase II Clinical Trial of Selinexor in Patients with Advanced Thymoma and Thymic Carcinoma.

8114 Background: Thymomas (T) and thymic carcinomas (TC) are rare thymic epithelial tumors (TET). Effective treatment options are needed for patients with progressive disease after platinum-based chemotherapy. Preclinical studies demonstrated antitumor activity of selinexor, an oral selective inhibitor of nuclear export (SINE) targeting exportin 1 (XPO1/CRM1), supporting the clinical development of XPO1 targeted therapy for the treatment of TET. To further assess the safety and efficacy of selinexor in TET, we conducted two parallel phase II clinical trials. Methods: The study included two parallel almost identical phase II trials conducted in the U.S. (NCT03193437), and Europe (Denmark and France; NCT03466827). Analysis was performed on data pooled from both trials. Both trials were non-randomized, open-label, two-armed phase II trials (Arm A: thymoma, Arm B: thymic carcinoma) with the same study design. Patients with histologically confirmed, advanced, inoperable TETs who had progressive disease after treatment with at least one platinum-containing chemotherapy regimen were included. In each 4-week cycle, patients received selinexor 60 mg twice weekly for 3 weeks. Due to poor tolerability, the starting dose was reduced to 40 mg twice weekly during the study. The primary objective was overall response rate (ORR) assessed by RECIST 1.1, with secondary objectives including progression free survival (PFS), overall survival (OS), and adverse events (AEs) assessed per CTCAE v4.03. Results: A total of 31 patients were enrolled in the study: 16 with T and 15 with TC. The median age was 57 years (range: 41-81), with 17 men and 14 women. The median number of prior systemic therapies was 2 (range: 1-9). The starting dose was 60 mg twice weekly for 29 (93.5%) patients, and 40 mg twice weekly for 2 (6.5%) patients. There was one complete response in the TC group (ORR 6.7%; 95% CI: 1.2-29.8%) and two partial responses (ORR 12.5% 95% CI: 3.5-36.0%) in the T group. Stable disease as the best response was observed in 11 (68.6%) patients with T and 12 (80%) patients with TC. The median duration of selinexor therapy was 4.5 months (mo) (range: 0.1-44.3). The most common treatment-related adverse events (TRAEs) were nausea (83.8%), vomiting (45.2%), anemia (41.9%), and fatigue (38.7%). The most common grade 3 or higher TRAEs were anemia (16.1%), thrombocytopenia (12.9%), and asthenia (9.7%). Twenty (64.5%) patients required dose reductions due to AEs, and 20 (64.5%) required dose interruptions. Median PFS was 7.8 mo (95% CI: 4.3 – 15.5) in the TC group and 13.6 mo (95% CI: 6.3 – 44.3) in the T group. Median OS was 15.5 mo (95% CI: 13.0-29.9) in the TC group and not reached in the T group. Due to low ORR, the trials did not proceed to the planned second phase. Conclusions: Selinexor demonstrated modest anticancer activity in patients with pretreated advanced TET. ORRs were low but prolonged stable disease was noted in a subset of patients. Clinical trial information: NCT03193437 and NCT03466827 .