Phase 2 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Gastric Cancer Cohort.

PURPOSE:E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor eribulin, and has shown preliminary efficacy in the treatment of gastric cancer (GC). Study 120, a phase 1b/2 open-label study, assessed efficacy and safety of E7389-LF in combination with nivolumab, a programmed cell death (PD)-1 inhibitor. This report focuses on the GC cohort of the expansion part. PATIENTS AND METHODS:Eligible patients had unresectable, measurable GC, and progression following a platinum drug plus fluoropyrimidine (1L) and a taxane-containing regimen (2L). The primary objective of the expansion phase was ORR, secondary objectives included safety and PFS, and exploratory objectives included OS and biomarker evaluation. Patients received E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks, both as intravenous infusions. Tumor responses were assessed every 6 weeks by the investigators per RECIST v1.1. Plasma and tumor biomarkers were assessed. RESULTS:In the 31 patients who received E7389-LF in combination with nivolumab, ORR was 25.8% (95% CI 11.9-44.6). The median PFS was 2.69 months (95% CI 1.91-2.99) and median OS was 7.85 months (95% CI 4.47-not estimable). The most common treatment-related TEAEs of any grade were neutropenia (77.4%), leukopenia (74.2%), and decreased appetite (51.6%). E7389-LF in combination with nivolumab significantly increased CD8-positive cells at C2D1 (P=0.039), and 6 of 7 vascular markers and 4 interferon-gamma-related markers showed increases from C1D1. CONCLUSIONS:Promising antitumor activity was observed with E7389-LF in combination with nivolumab in patients with GC, and no new safety signals were observed, compared with either monotherapy.