Abstract 1398
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:
348P
Eribulin formulation/dose | Plasma AUC (h*ng/mL) of eribulin | |
---|---|---|
Total | Unbound | |
E7389-LF 1.0 mg/m2 | 26300 | 98.1 |
E7389-LF 1.5 mg/m2 | 34700 | 120 |
E7389-LF 2.0 mg/m2 | 39100 | 148 |
Standard eribulin 1.4 mg/m2 | 673 | 336 |
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.
Editorial acknowledgement
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.
Resources from the same session
3907 - Exploration of efficacious alternative regorafenib regimens to manage hand-foot-skin-reaction (HFSR)
Presenter: Axel Grothey
Session: Poster Display session 2
Resources:
Abstract
3958 - Quality of Life (QoL) in Metastatic Colorectal Cancer (mCRC) in the Real World: Final Results of a European Survey
Presenter: Zorana Maravic
Session: Poster Display session 2
Resources:
Abstract
3563 - BISQUIT: A Randomized Phase II Study of the Administration of Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy for Patients With Squamous Cell Carcinoma of the Anal Canal
Presenter: Rachel Riechelmann
Session: Poster Display session 2
Resources:
Abstract
1184 - iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer
Presenter: Fiona Turkes
Session: Poster Display session 2
Resources:
Abstract
3346 - Phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): The AVANA Study
Presenter: Lisa Salvatore
Session: Poster Display session 2
Resources:
Abstract
3895 - A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study.
Presenter: Maria Aurelia Barbera
Session: Poster Display session 2
Resources:
Abstract
2012 - Open Label Phase III Study of Arfolitixorin vs. Leucovorin in mFOLFOX-6 for First Line Treatment of Metastatic Colorectal Cancer: AGENT
Presenter: Josep Tabernero
Session: Poster Display session 2
Resources:
Abstract
2198 - SOLSTICE, a phase 3, randomized, open label study of trifluridine/tipiracil+bevacizumab (bev) versus capecitabine+bev for the 1L treatment of patients with unresectable metastatic colorectal cancer (mCRC) who are not candidates for intensive therapy
Presenter: Thierry Andre
Session: Poster Display session 2
Resources:
Abstract
2921 - A Phase Ib/ II Trial to Assess the Safety and Efficacy of CXD101 in Combination with the PD-1 Inhibitor Nivolumab in Patients with Metastatic, Previously-Treated, Microsatellite-Stable (MSS) Colorectal Carcinoma (short title CAROSELL)
Presenter: Mark Saunders
Session: Poster Display session 2
Resources:
Abstract
3695 - A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation
Presenter: Heinz Josef Lenz
Session: Poster Display session 2
Resources:
Abstract