Phase I Study of the Liposomal Formulation of Eribulin (E7389-LF): Results from the Advanced Gastric Cancer Expansion Cohort.

Nozomu Machida, Kensei Yamaguchi, Angela Teng, Bob Zimmermann, Taro Semba, Takao Takase, Shiori Okumura, Takuya Suzuki, Satoshi Yuki, Kohei Shitara, Kan Yonemori, Takuya Hamakawa, Yasuyoshi Sato, Akihito Kawazoe, Yoshito Komatsu, Takashi Oshima, Satoru Iwasa, Motohiro Hirao

Journal: Clinical cancer research : an official journal of the American Association for Cancer Research 2023;29(8):1460-1467

PMID: 36730323

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Abstract

PURPOSE

In the dose-expansion part of this open-label, phase I study, we explored the efficacy and safety of E7389-LF (liposomal formulation of eribulin) in Japanese patients with advanced gastric cancer.

PATIENTS AND METHODS

Patients with advanced gastric cancer who had been previously treated with ≥2 lines of chemotherapy received E7389-LF 2.0 mg/m2 every 3 weeks (the previously determined maximum tolerated dose, the primary objective of Study 114). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), and safety; exploratory objectives included disease control rate (DCR) and clinical benefit rate (CBR), as well as pharmacodynamic measurements of serum biomarkers.

RESULTS

As of June 24, 2021, 34 patients were enrolled and treated (10 from the original dose-expansion cohort, expanded to include 24 additional patients). Six patients had partial responses, for an ORR of 17.6% [95% confidence interval (CI), 6.8-34.5], and the median PFS was 3.7 months (95% CI, 2.7-4.8). The DCR was 79.4% (95% CI, 62.1-91.3), and the CBR was 32.4% (95% CI, 17.4-50.5). Overall, 32 patients (94.1%) experienced treatment-related adverse events, and 26 patients (76.5%) experienced grade ≥3 events, most commonly neutropenia (41.2%) and leukopenia (29.4%). Of the 8 endothelial cell/vasculature markers tested in this study, 7 were significantly increased among patients treated with E7389-LF; these changes were generally consistent regardless of best overall response.

CONCLUSIONS

E7389-LF 2.0 mg/m2 every 3 weeks was tolerable and showed preliminary activity for the treatment of patients with gastric cancer.

Address: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Canter Hospital East, Kashiwa, Japan.; Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan.; Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.; Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan.; Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Hokkaido, Japan.; Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.; Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.; Department of Gastroenterology and Medical Oncology, Kanagawa Cancer Center, Kanagawa, Japan.; Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.; Japan and Asia Clinical Development Department, Oncology Business Group, Eisai Co., Ltd., Tokyo, Japan.; Clinical Data Science Department, Medicine Development Center, Eisai Co., Ltd., Tokyo, Japan.; Tsukuba Research Department, Oncology Business Group, Eisai Co., Ltd., Ibaraki, Japan.; Translational Science, Oncology Business Group, Eisai Inc., Nutley, New Jersey.; Biostats, Oncology Business Group, Eisai Inc., Nutley, New Jersey.; Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

DOI: 10.1158/1078-0432.CCR-22-3027