Background

Eribulin is approved for treatment of advanced/metastatic breast cancer and previously treated, unresected liposarcoma. E7389-LF is a liposomal formulation of eribulin. The maximum tolerated dose (MTD) in a prior phase 1 study was 1.4 mg/m² Q3W or 1.5 mg/m² Q2W.

Methods

The primary objective was to determine MTD and compare the tolerability of higher (> prior) Q3W doses vs the prior Q2W dose. E7389-LF was administered (3 + 3 design) intravenously Q3W (day 1 of a 21-day cycle) and Q2W (days 1 and 15 of a 28-day cycle) to solid tumor pts in Japan for which no alternative standard or effective therapy exists. Planned dose ranges were 1.0-2.5 mg/m² Q3W and 1.0-1.5 mg/m² Q2W.

Results

21 pts were enrolled; 3, 3 and 6 pts in 1.0, 1.5 and 2.0 mg/m² Q3W; 3 and 6 pts in 1.0 and 1.5 mg/m² Q2W, respectively. 10 pts were male, median age was 58 years (range, 22-68), and 11 had ECOG-PS 0. One dose-limiting toxicity was observed in the 2.0 mg/m² Q3W group (febrile neutropenia; n = 6); thus, 2.5 mg/m² Q3W was not assessed. Adverse events ≥ grade 3 included neutropenia (67%), leukopenia (48%), anemia (19%), increased ɣ-glutamyltransferase, lymphopenia, and thrombocytopenia (each 14%). The MTDs were 2.0 mg/m² Q3W and 1.5 mg/m² Q2W. Partial response was noted in 4 pts (19%) with esophageal squamous cell carcinoma, adenoid cystic carcinoma, urothelial cancer, and small cell carcinoma of the cervix. Area-under-the-curve (AUC) values of total eribulin were higher and AUC of unbound eribulin in plasma lower with E7389-LF vs the standard dose of eribulin (Table).Table:

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Conclusions

E7389-LF was well tolerated in Japanese pts with advanced solid tumors with antitumor effects in several tumor types. Plasma AUC of eribulin after administration of E7389-LF suggested a promising exposure profile of the liposomal formulation in humans. The 2.0 mg/m² Q3W regimen was recommended for further investigation in an expansion cohort of specific tumor types.

Clinical trial identification

NCT03207672.

Legal entity responsible for the study

Eisai Co., Ltd.

Funding

Eisai Co., Ltd.

Disclosure

N. Yamamoto: Research grant / Funding (institution): Chugai, Taiho, Eisai, Lilly, Quintiles, Astellas, BMS, Novartis, Daiichi-Sankyo, Pfizer, Boehringer Ingelheim, Kyowa-Hakko Kirin, ONO Pharmaceutical Co. LTD, Takeda, Janssen Pharma, MSD, Merck; Honoraria (self): ONO Pharmaceutical Co. LTD, Chugai, AstraZeneca, Pfizer, Lilly, BMS; Advisory / Consultancy: Eisai, Otsuka, Takeda, Boehringer Ingelheim, Cimic. S. Iwasa: Research grant / Funding (institution), grants from Eisai, during the conduct of the study: Eisai, Eli Lilly, Chugai, Novartis, Merck-Serono, Daiichi-Sankyo, Bristol-Myers Squibb, Bayer; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly, Taiho, Chugai, ONO Pharmaceutical Co., LTD. A. Shimomura: Travel / Accommodation / Expenses, personal fees: Chugai; Travel / Accommodation / Expenses, personal fees: Novartis; Travel / Accommodation / Expenses, personal fees: Pfizer; Travel / Accommodation / Expenses, personal fees: Nippon Kayaku; Travel / Accommodation / Expenses, personal fees: AstraZeneca; Travel / Accommodation / Expenses, personal fees: Eisai. S. Kondo: Research grant / Funding (institution): ASLAN Pharmaceuticals; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Pfizer. K. Yonemori: Research grant / Funding (self), trail management at site: Eisai; Honoraria (self): Eisai. Y. Fujiwara: Research grant / Funding (institution): Abbvie, AstraZeneca, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Incyte, Merck Serono, Novartis; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Taiho, Sysmex, ONO, Novartis, MSD, Chugai, BMS, AstraZeneca; Advisory / Consultancy: MSD, ONO, AstraZeneca, BMS. T. Shimizu: Research grant / Funding (institution): Novartis, Eli Lilly, Bristol-Myers Squibb, Daiichi-Sankyo, Millenium-Takeda, AbbVie, AstraZeneca, Eisai, PharmaMar, 3D-Medicine, Symbio Pharmaceuticals, Chordia Therapeutics, Five Prime; Advisory / Consultancy: The Consortium on Harmonization of Institutional Requirements for Clinical Research (CHAIR) Joint Scientific Committee Review Member for Phase 1 trials in Hong Kong. All other authors have declared no conflicts of interest.