Data from Phase 1b/2 Study of a Liposomal Formulation of Eribulin (E7389-LF) Plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase 1b

<div>Abstract<p>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. Patients and Methods: 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/m2 plus nivolumab 360 mg every 3 weeks (Q3W), E7389-LF 2.1 mg/m2 plus nivolumab 360 mg Q3W, E7389-LF 1.1 mg/m2 plus nivolumab 240 mg every 2 weeks (Q2W), or E7389-LF 1.4 mg/m2 plus nivolumab 240 mg Q2W. Primary objectives were to evaluate the safety/tolerability of each dose cohort and to determine the recommended phase 2 dose (RP2D). Secondary/exploratory objectives, including safety (dose-limiting toxicities [DLTs] and adverse events [AEs]), 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/mg2 Q3W [n=6], E7389-LF 2.1 mg/m2 Q3W [n=6], E7389-LF 1.1 mg/m2 Q2W [n=7], E7389-LF 1.4 mg/m2 Q2W [n=6]). Twenty-four patients were evaluated for DLTs, of whom 3 had DLTs (1 at E7389-LF 1.7 mg/m2 Q3W, 1 at 1.1 mg/m2 Q2W, and 1 at 1.4 mg/m2 Q2W). All patients had ≥1 treatment related treatment-emergent AE (TEAE); 68.0% had ≥1 grade 3-4 treatment-related TEAE. Changes in vasculature and interferon-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 studies was 2.1 mg/m2 plus nivolumab 360 mg Q3W.</p></div>