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

Abstract

Purpose: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor eribulin and has shown preliminary efficacy in the treatment of gastric cancer. Study 120, a phase Ib/II 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 gastric cancer cohort within the expansion phase.

Patients and methods: Eligible patients had unresectable, measurable gastric cancer, progression following a platinum drug plus fluoropyrimidine (1L), and a taxane-containing regimen (2L). The primary objective of the expansion phase was objective response rate, secondary objectives included safety and PFS, and exploratory objectives included overall survival 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, the objective response rate was 25.8% [confidence interval (CI), 11.9-44.6]. The median progression-free survival was 2.69 months (95% CI, 1.91-2.99) and median overall survival was 7.85 months (95% CI, 4.47-not estimable). The most common treatment-related TEAE 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 six of seven vascular markers and four IFNγ-related markers showed increases from C1D1.

Conclusions: Promising antitumor activity was observed with E7389-LF in combination with nivolumab in patients with gastric cancer, and no new safety signals were observed, compared with either monotherapy.

Trial registration: ClinicalTrials.gov NCT04078295.

Figure 1.

Percentage change in sums of diameters of target lesions from baseline over time (A)^a, and by PD-L1 CPS at nadir (B). ^aPatients could continue to receive study drugs beyond disease progression if they had investigator-assessed clinical benefit and were tolerating study drugs. Part A includes data from beyond disease progression. One patient was excluded from the overall group of part B, as change from baseline could not calculated; at their week 3 assessment, their target lesion was not evaluable, but their nontarget lesion showed progressive disease. N/A, not available.

Figure 2.

PFS as assessed by investigator per RECIST v1.1 (A) and OS (B). Medians were estimated by the Kaplan–Meier method, and the 95% CI were calculated based on the Greenwood formula and log–log transformation. NE, not estimable.

Figure 3.

Biomarker assessments: depiction of immune phenotypes (A), analysis of changes in immune phenotypes (B), tumor-infiltrating lymphocytes (C), and microvessel density (D) from screening to C2D1; and pharmacodynamic changes in plasma biomarkers from C1D1 to C5D1 by tumor response status (E). Wilcoxon signed-rank test P values: *, P < 0.05; **, P < 0.01; ***, P < 0.001; for part E, P values represent comparison with baseline values at each timepoint. Patient numbers at each timepoint are: C1D1: n = 31, C1D8: n = 31, C1D15: n = 30, C2D1: n = 29, C2D8: n = 29, C2D15: n = 26, C3D1: n = 22, C4D1: n = 21, C5D1: n = 12. C#D#, cycle # day #.