Phase 1 study of the liposomal formulation of eribulin (E7389-LF): Results from the advanced gastric cancer expansion cohort.
Authors: Yamaguchi Kensei , Iwasa Satoru , Hirao Motohiro , Oshima Takashi , Harada Kazuaki , Sato Yasuyoshi , Kawazoe Akihito , Yonemori Kan , Nishikawa Kazuhiro , Machida Nozomu , Komatsu Yoshito , Suzuki Takuya , Okumura Shiori , Nagai Reiko , Takase Takao , Shitara Kohei 
Published: June 2021

4025 Background: Eribulin has proven efficacy in previously treated metastatic breast cancer and liposarcoma. E7389-LF is a new formulation that uses liposomes to encapsulate eribulin, which is anticipated to improve eribulin concentration in tumor tissues. In the dose-expansion part of a phase 1 study of E7389-LF, the safety profile was acceptable and 2 patients (pts) out of 10 with gastric cancer (GC) had an objective response. Thus, the GC cohort was expanded for further evaluation. Here, we report efficacy and safety data from the phase 1 expansion cohort of pts with advanced GC who were treated with E7389-LF. Methods: Eligible pts were those with GC who had no alternative standard or effective therapy options after ≥2 prior chemotherapy regimens. Target total enrollment was 32 pts (10 pts in the initial GC cohort plus an additional 22 pts in the expanded cohort). E7389-LF 2.0 mg/m2 was administered intravenously once every 3 weeks. Tumor responses were assessed every 6 weeks (± 1 week) by RECIST v1.1. Results: At data cutoff (Oct 16, 2020), 34 pts with GC were enrolled (10 pts in the initial GC cohort; 24 pts in the expanded GC cohort) with a median of 5 prior therapies (range, 2–11). Previous immune checkpoint inhibitor (ICI) therapy was reported for 26 (76.5%) pts. All pts were evaluable for objective response rate (ORR) and progression-free survival (PFS), and 30 pts were evaluable for overall survival (OS). Among all pts with GC, the ORR was 17.6% (95% CI 6.8–34.5) and the disease control rate was 79.4% (95% CI 62.1–91.3). Median PFS was 3.7 months (95% CI 2.7–4.3) and median OS was 7.6 months (95% CI 6.7–15.4). The ORRs were 19.2% (95% CI 6.6–39.4) in ICI-pretreated pts and 12.5% (95% CI 0.3–52.7) in pts without prior ICI therapy. Median PFS was similar regardless of prior treatment with ICIs (3.7 months [95% CI 2.7–5.6] in ICI-pretreated pts vs 3.4 months [95% CI 1.0–4.3] in pts without prior ICI therapy); however, the PFS rate at 6 months in ICI-pretreated pts was higher vs the rate in pts without prior ICI therapy (35.9% [95% CI 17.2–55.1] vs 0%, respectively). Median OS was also longer in ICI-pretreated pts (evaluable pts, n = 23) vs pts without prior ICI therapy (evaluable pts, n = 7) (10.0 months [95% CI 6.7–not estimable] vs 6.7 months [95% CI 3.1–8.5], respectively). Common grade ≥3 adverse events included neutropenia (41.2%), leukopenia (29.4%), and anemia (26.5%). In cycle 1, there were no cases of febrile neutropenia among the 22 pts treated with prophylactic peg-GCSF; among pts who did not receive prophylactic peg-GCSF, 16.7% of pts had febrile neutropenia. Conclusions: E7389-LF had a manageable safety profile and encouraging activity in pts with heavily treated GC. In pts with GC, prior treatment with ICIs might enhance the potential efficacy of E7389-LF. These results support further development of E7389-LF for advanced GC. Clinical trial information: NCT03207672.