The esophageal cancer cohort of a phase 2 trial of E7389-LF (liposomal formulation of eribulin) + nivolumab.
Authors: Ooki Akira , Yamamoto Sachiko , Kawakami Hisato , Makino Tomoki , Kawazoe Akihito , Masuishi Toshiki , Tsushima Takahiro , Hirao Motohiro , Takegawa Naoki , Hino Kaori , Iwasa Satoru , Hara Hiroki , Sumiyoshi Naoki , Matsuoka Daiko , Otake Yohei , Yasuda Keisuke , Takase Takao , Takashima Shuya , Semba Taro , Oshima Takashi 
Published: January 2023

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Background: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor, eribulin. Treatment with E7389-LF plus the programmed cell death 1 inhibitor nivolumab may result in an increased antitumor effect through vascular remodeling. The phase 1b part of the open-label Study 120 assessed dosing and safety of E7389-LF combined with nivolumab in patients (pts) with solid tumors; the phase 2 part assessed efficacy and safety in expansion cohorts, including an esophageal cancer (EGC) cohort. Methods: For the EGC cohort in the phase 2 part of Study 120, pts were required to have unresectable, measurable (by RECIST v1.1) EGC lesion(s) that showed progression during or after first-line chemotherapy with no other systemic chemotherapy. The primary objective of the phase 2 part was to assess objective response rate (ORR), with success defined as Bayesian posterior probability over 85% beyond threshold (20%) for best overall response (ie, 9 responders of planned 32 pts enrolled). Secondary objectives included assessment of safety and progression-free survival (PFS). The recommended phase 2 dosing regimen was previously determined to be E7389-LF 2.1 mg/m2 every 3 weeks (Q3W) plus nivolumab 360 mg Q3W. Tumor assessments were performed by RECIST v1.1 every 6 weeks. All adverse events (AEs) were monitored and recorded. Results: In the EGC cohort, 35 pts were included. Most pts (88.6%) were male, and the median age was 69.0 years (range 47–85). At data cutoff (May 31, 2022), 5 pts (14.3%) were still undergoing treatment. Discontinuations occurred in 30 pts (85.7%)—25 (71.4%) due to disease progression, 4 (11.4%) due to an adverse event, and 1 (2.9%) due to patient preference. ORR with E7389-LF + nivolumab was 22.9% (95% CI 10.4–40.1) and the disease control rate (DCR) was 62.9% (95% CI 44.9–78.5). Median PFS was 2.81 months (95% CI 1.31–4.17) and the 6-month PFS rate was 20.2% (95% CI 8.7–35.0). Median OS was not reached (95% CI 6.54–not estimable), and the 6-month OS rate was 71.4% (95% CI 53.4–83.5). Treatment-related treatment-emergent (TE) AEs of any grade and of grade ≥3 occurred in 94.3% and 80.0% of pts, respectively. The most common treatment-related TEAEs of any grade were neutropenia (65.7%), leukopenia (57.1%), and decreased appetite (45.7%). The most common treatment-related TEAEs of grade ≥3 were neutropenia (54.3%), leukopenia (34.3%), and febrile neutropenia (22.9%). TEAEs led to dose reduction of E7389-LF in 17 pts (48.6%). TEAEs led to withdrawal of either E7389-LF or nivolumab in 5 pts (14.3%): pneumonia (n=2), traumatic hemothorax (n=1), acute kidney injury (n=1), and pneumonitis (n=1). Conclusions: E7389-LF combined with nivolumab showed an ORR of 22.9% in pts with EGC. Despite this modest ORR, the DCR of 62.9% was notable. No new safety signals were observed compared to the known profiles of each monotherapy. Clinical trial information: NCT04078295 .