Dose Escalation Data from the Phase 1 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors

PURPOSE: We report the dose-escalation part of a phase I study of liposomal eribulin (E7389-LF) in Japanese patients with advanced solid tumors and no alternative standard therapy. PATIENTS AND METHODS: Patients ≥20 years old were enrolled. E7389-LF doses of 1.0 to 1.5 mg/m(2) once every two weeks (Q2W) or 1.0 to 2.5 mg/m(2) once every three weeks (Q3W) were planned. The primary objective was to determine the MTD by evaluating dose-limiting toxicities (DLT). Secondary objectives included safety/tolerability assessments, objective response rate (ORR), and progression-free survival; serum biomarker assessment was an exploratory objective. RESULTS: Twenty-one patients were enrolled and treated; 12 in the Q3W group (1.0 mg/m(2), n = 3; 1.5 mg/m(2), n = 3; 2.0 mg/m(2), n = 6) and 9 in the Q2W group (1.0 mg/m(2), n=3; 1.5 mg/m(2), n = 6). The Q3W and Q2W MTDs were 2.0 mg/m(2) and 1.5 mg/m(2), respectively. One patient receiving 2.0 mg/m(2) Q3W had a DLT of grade 3 febrile neutropenia. The most common grade 3 treatment-emergent adverse events were neutropenia (66.7% in Q3W and Q2W) and leukopenia (Q3W, 58.3%; Q2W, 33.3%). One patient in the Q3W group (2.0 mg/m(2)) and 3 in the Q2W group (1.0 mg/m(2), n = 1; 1.5 mg/m(2), n = 2) achieved a partial response [overall ORR, 19.0%; 95% confidence interval (CI), 5.4–41.9]. Endothelial [TEK receptor tyrosine kinase (TEK), intercellular adhesion molecule 1 (ICAM1), vascular endothelial growth factor receptor 3 (VEGFR3), platelet/endothelial cell adhesion molecule 1 (PECAM1)], vasculature (collagen IV), and immune-related [interferon gamma (IFNγ), C-X-C motif chemokine ligand 11 (CXCL11), C-X-C motif chemokine ligand 10 (CXCL10)] biomarker levels were increased. CONCLUSIONS: E7389-LF was well tolerated at 2.0 mg/m(2) Q3W and 1.5 mg/m(2) Q2W. Considering the toxicity profile of both regimens, the recommended dose was 2.0 mg/m(2) Q3W. Expansion cohorts are ongoing.