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
4250 - Phase II study of avelumab in combination with cetuximab as a rechallenge strategy in pre-treated RAS wild type metastatic colorectal cancer patients: CAVE (cetuximab-avelumab) Colon.
Presenter: Erika Martinelli
Session: Poster Display session 2
Resources:
Abstract
5234 - The ORCHESTRA trial; A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).
Presenter: Lotte Bakkerus
Session: Poster Display session 2
Resources:
Abstract
5294 - EMERGE: Epigenetic Modulation of the Immune Response in Gastrointestinal cancers
Presenter: Elizabeth Cartwright
Session: Poster Display session 2
Resources:
Abstract
913 - Phase III, international, multicenter, randomized, open-label trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) alone for surgically resected pancreatic adenocarcinoma (APACT): subgroup analyses
Presenter: Margaret Tempero
Session: Poster Display session 2
Resources:
Abstract
1668 - FOLFIRINOX in locally advanced (LA) and borderline resectable (BR) pancreatic adenocarcinoma : update of the AGEO cohort.
Presenter: Edouard Auclin
Session: Poster Display session 2
Resources:
Abstract
2559 - Impact of adjuvant treatment with nab-paclitaxel and gemcitabine (nab-P+GEM) vs gemcitabine alone (GEM) on health-related quality of life (QoL) in patients (pts) with surgically resected pancreatic adenocarcinoma (PA) in the Adjuvant Pancreatic Adenocarcinoma Clinical Trial (APACT)
Presenter: Hanno Riess
Session: Poster Display session 2
Resources:
Abstract
4897 - Early detection of pancreatic ductal adenocarcinoma using methylation signatures in circulating tumor DNA
Presenter: Xiao-ding Liu
Session: Poster Display session 2
Resources:
Abstract
1755 - Evaluation of minimal important difference (MID) for the European Organisation for Research and Treatment of Cancer (EORTC) Pancreatic Cancer Module (PAN26) in patients with surgically resected pancreatic adenocarcinoma
Presenter: Michele Reni
Session: Poster Display session 2
Resources:
Abstract
2876 - Multispectral analysis of lymphocyte complexity in periampullary adenocarcinoma
Presenter: Sebastian Lundgren
Session: Poster Display session 2
Resources:
Abstract
1902 - Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)
Presenter: Jae Ho Jeong
Session: Poster Display session 2
Resources:
Abstract