Phase 1b/2 study of the liposomal formulation of eribulin (E7389-LF) in combination with nivolumab: Results from the phase 2 esophageal cancer cohort

Abstract

Background: Esophageal cancer is one of the most common types of cancer in Japan. Herein, we report the efficacy and safety of E7389-LF plus the immune checkpoint inhibitor, nivolumab, from the esophageal cancer cohort of the phase 2 part of Study 120.

Methods: Eligible patients received E7389-LF 2.1 mg/m² plus nivolumab 360 mg intravenously Q3W. The primary objective was to evaluate the objective response rate (ORR); other objectives included safety, progression-free survival (PFS), and overall survival (OS).

Results: Of the 35 Japanese patients enrolled, 7 (20.0%) had a partial response as their best overall response, and 14 (40.0%) had stable disease. The ORR was 20.0% (95% CI 8.4-36.9). The duration of response was 5.6 months (95% CI 1.7-not estimable [NE]). The median PFS was 2.81 months (95% CI 1.31-4.17). The median OS was not reached (95% CI 6.54 months-NE). The most common treatment-emergent adverse events were neutropenia (65.7%), pyrexia (60.0%), and leukopenia (57.1%). Select plasma endothelial cell markers levels increased from day 1 of cycle 1 and changes were pronounced between days 8-15 of each cycle.

Conclusions: E7389-LF plus nivolumab showed antitumor activity in patients with unresectable and pretreated esophageal cancer and should be evaluated further in a broader population.

Clinical trial registration: NCT04078295.

Fig. 1. Changes in sums of diameters in target lesions from baseline over time.

Patients with disease progression are included. Patients could continue to receive study drugs beyond disease progression if they had investigator-assessed clinical benefits and were tolerating the study drugs.

Fig. 2. Change in tumor lesion size from baseline to postbaseline Nadir by PD-L1 CPS.

Changes are reported in evaluable patients overall, evaluable patients who had a fresh biopsy sample available, and evaluable patients who were assessed based on an archival tissue sample. ^aOf the 35 patients enrolled, 1 was excluded from the waterfall plot as they had a tumor response of progressive disease (the target lesion was not evaluable) at their first assessment, and another patient was excluded because of tumor size data post-drug administration. CPS combined positive score, N/A not available, PD-L1 programmed cell death ligand 1.

Fig. 3. Kaplan–Meier survival curves.

a PFS per RECIST v1.1 by Investigator Assessment. b OS. CI confidence interval, OS overall survival, PFS progression-free survival, RECIST v1.1 Response Evaluation Criteria In Solid Tumors version 1.1.