Phase 1, open-label, dose-escalation study of sorafenib in combination with eribulin in patients with advanced, metastatic, or refractory solid tumors

Combining sorafenib and eribulin mesylate may provide synergistic antitumor activities with limited overlapping toxicities. This phase 1b, open-label, dose-escalation study evaluated safety, pharmacokinetics, maximum tolerated dose/recommended phase 2 dose (MTD/RP2D), and preliminary efficacy of sorafenib plus standard-dose eribulin mesylate in patients with advanced, metastatic, or refractory tumors. Patients received sorafenib 200 mg twice daily (BID; n = 5), 600 mg/day (n = 8), and 400 mg BID (MTD; n = 27). Dose-limiting toxicities were increased alanine aminotransferase and acute coronary syndrome (both grade 3) in the 400-mg BID dose-escalation and expansion cohorts, respectively. No significant increase in mean QTcF duration was observed with eribulin plus sorafenib versus eribulin alone; there were no drug–drug interactions. Five patients achieved partial response; 16 achieved stable disease. The combination of sorafenib and eribulin mesylate presented no unexpected safety concerns and no significant impact on QT/QTc intervals or drug–drug interactions. Sorafenib 400 mg BID plus standard-dose eribulin is the RP2D.