Phase Ib/II Study of a Liposomal Formulation of Eribulin (E7389-LF) plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase Ib

PURPOSE: To determine a recommended dose of liposomal eribulin (E7389-LF) in combination with nivolumab in patients with advanced solid tumors, and to evaluate the safety, efficacy, pharmacokinetics, and biomarker impact of this regimen. EXPERIMENTAL DESIGN: Japanese patients with advanced, nonresectable, or recurrent solid tumors and no existing alternative standard/effective therapy (except nivolumab monotherapy) were assigned to either E7389-LF 1.7 mg/m(2) plus nivolumab 360 mg every 3 weeks, E7389-LF 2.1 mg/m(2) plus nivolumab 360 mg every 3 weeks, E7389-LF 1.1 mg/m(2) plus nivolumab 240 mg every 2 weeks, or E7389-LF 1.4 mg/m(2) plus nivolumab 240 mg every 2 weeks. Primary objectives were to evaluate the safety/tolerability of each dose cohort and to determine the recommended phase II dose (RP2D). Secondary/exploratory objectives, including safety [dose-limiting toxicities (DLT) and adverse events (AE)], pharmacokinetics, efficacy [including objective response rate (ORR)], and biomarker results were used in determining the RP2D. RESULTS: Twenty-five patients were enrolled to treatment [E7389-LF 1.7 mg/mg(2) every 3 weeks (n = 6), E7389-LF 2.1 mg/m(2) every 3 weeks (n = 6), E7389-LF 1.1 mg/m(2) every 2 weeks (n = 7), E7389-LF 1.4 mg/m(2) every 2 weeks (n = 6)]. Twenty-four patients were evaluated for DLTs, of whom 3 had DLTs (1 at E7389-LF 1.7 mg/m(2) every 3 weeks, 1 at 1.1 mg/m(2) every 2 weeks, and 1 at 1.4 mg/m(2) every 2 weeks). All patients had ≥1 treatment-related treatment-emergent AE (TEAE); 68.0% had ≥1 grade 3–4 treatment-related TEAE. Changes in vasculature and IFN-related biomarkers were seen in each cohort. The overall ORR was 16%. CONCLUSIONS: E7389-LF plus nivolumab was tolerable overall; the recommended dose for future study was 2.1 mg/m(2) plus nivolumab 360 mg every 3 weeks. SIGNIFICANCE: This phase Ib part of a phase Ib/II study assessed the tolerability and activity of a liposomal formulation of eribulin (E7389-LF) plus nivolumab in 25 patients with advanced solid tumors. The combination was tolerable overall; 4 patients had a partial response. Vasculature and immune-related biomarker levels increased, suggesting vascular remodeling.