eribulin + selinexor

The combination of eribulin and selinexor is an investigational treatment that has been studied primarily for advanced solid tumors and triple-negative breast cancer (TNBC). This combination has shown promising antitumor activity, particularly in some patients with TNBC. ## Mechanism of Action Selinexor (KPT-330) is a potent inhibitor of exportin 1 (XPO1), which inhibits tumor growth[1][3]. Eribulin is a microtubule inhibitor that has established efficacy in various cancers. Preclinical studies demonstrated that selinexor enhances the antitumor efficacy of eribulin in triple-negative breast cancer in vitro and in vivo[1][3]. ## Clinical Development A phase 1b trial was conducted using a 3+3 dose-escalation design to evaluate the combination in patients with advanced solid tumors, with a specific dose-expansion cohort for TNBC patients[1][2]. The study enrolled 31 patients, including 19 with TNBC, 9 with sarcoma, and 3 with other cancers[1][3]. **Safety Profile:** - Most common treatment-related adverse events included nausea (77%), leukopenia (77%), anemia (68%), neutropenia (68%), and fatigue (48%)[1] - One dose-limiting toxicity occurred at the first dose level with prolonged grade 3 neutropenia[1] - The combination was found to be safe with a manageable toxicity profile[3] - Dose reductions were required in some patients[5] **Efficacy Results:** - The objective response rate (ORR) was 10% overall[1] - In the TNBC dose-expansion cohort, the ORR was 11%[1] - Two confirmed partial responses were observed with durations of 10.8 and 19.1 months (one ongoing at the time of reporting)[1] - Durable responses and disease control were observed in metastatic TNBC patients[3] **Recommended Phase 2 Dose:** The recommended phase 2 dose was established as 80 mg of selinexor orally once per week and 1 mg/m² eribulin administered intravenously on days 1 and 8 every 3 weeks[1]. ## Current Status The combination showed modest overall clinical efficacy with some durable responses, particularly in TNBC. Researchers concluded that further study is needed to examine the determinants of response to this combination[3].

Brand names

HalavenXpovio

Other names

eribulin mesylateselinexor