405P - E7389-LF as a first-line (1L) chemotherapy for patients (pts) with metastatic/advanced HER2-negative breast cancer (HER2− BC): Results from a phase I study dose-expansion part

Background

E7389-LF is a liposomal formulation of eribulin being tested as 1L chemotherapy in pts with advanced HER2− BC. In an open-label phase 1 study of E7389-LF, a dose-escalation part determined a recommended regimen of 2.0 mg/m² once every 3 weeks (Q3W). Here, we present efficacy and safety data from the dose-expansion part in Japanese pts with confirmed metastatic HER2− BC who had not received prior chemotherapy for locally advanced/metastatic disease.

Methods

E7389-LF was administered at 2.0 mg/m² Q3W until disease progression, development of unacceptable toxicity, or withdrawal of consent. Efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Tumors were assessed by investigators per RECIST v1.1. Additionally, a subanalysis was conducted in pts with luminal BC (hormone receptor-positive [HR+]) and in pts with triple-negative BC (TNBC) who were programmed-death ligand 1-negative (PD-L1−). Adverse events (AEs) were monitored and recorded, and serum biomarkers were explored.

Results

At the data cutoff date (October 26, 2022), of 26 pts who received E7389-LF, 10 (38.5%) had ongoing treatment; 16 pts discontinued due to either disease progression (13 [50%]), AEs (2 [7.7%]), or pt choice (1 [3.8%]). Median age was 59 y (range 35–77); 19 pts (73.1%) had ECOG-PS 0; 22 pts (84.6%) were HR+; 4 pts (15.4%) had TNBC and were PD-L1−. ORR was 30.8% overall (HR+: 27.3%; TNBC and PD-L1−: 50%). Median PFS was 8.1 months (95% CI 4.4–11.1). Median OS was not reached (95% CI not estimable). Treatment-emergent AEs (TEAEs) led to dose reduction in 15 pts and drug discontinuation in 2 pts. TEAEs of grade ≥3 occurred in 25 pts (96.2%), most commonly (>40%) neutropenia (n=20, 76.9%) and leukopenia (n=11, 42.3%). Of 7 pts given prophylactic pegylated granulocyte-colony stimulating factor (peg-GCSF), 0 developed febrile neutropenia (FN). Of the 19 pts without peg-GCSF, 2 (10.5%) had FN. Changes in vasculature- and IFNγ-related serum markers were noted.

Conclusions

E7389-LF showed promising efficacy and a manageable toxicity profile and should be explored as a 1L treatment option for pts with advanced HER2− BC.

Clinical trial identification

NCT03207672.

Editorial acknowledgement

Medical writing support was provided by Dolly Al Koborssy, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA.

Legal entity responsible for the study

Eisai Co., Ltd., Tokyo, Japan.

Funding

Eisai Inc., Nutley, NJ, USA.

Disclosure

K. Yonemori: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, yowa Hakko Kirin, Nihon Kayaku, Sanofi, Haihe; Financial Interests, Personal, Other, Consulting fees: Novartis, Eisai, AstraZeneca, Chugai , Takeda, Genmab, Sanofi, OncXerna; Financial Interests, Personal, Other, Lecture fee: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, MSD, FujiFilm Pharma, Bayer, Asteras, Boehringer Ingelheim, Daiichi Sankyo, Ono, Bristol Meyers, PDR pharma, Sanofi. Y. Miyoshi: Financial Interests, Personal, Speaker’s Bureau: Chugai, AstraZeneca, Eli Lilly, Pfizer, MSD, Daiichi Sankyo, Kyowa-Kirin, Taiho, Eisai; Financial Interests, Personal, Funding: Chugai, AstraZeneca, Eli Lilly, MSD, Daiichi Sankyo, Kyowa-Kirin, Taiho, Eisai. H. Yasojima: Non-Financial Interests, Institutional, Principal Investigator: Osaka National Hospital; Financial Interests, Institutional, Sponsor/Funding: Eisai; Financial Interests, Institutional, Principal Investigator: Eisai Co. Ltd.. J. Watanabe: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Advisory Role: Eisai. T. Takano: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Chugai, Eli Lilly; Financial Interests, Personal, Advisory Board: Eisai, Daiichi Sankyo, Gilead; Financial Interests, Institutional, Principal Investigator: Eisai, Daiichi Sankyo, Gilead, Chugai, AstraZeneca, Eli Lilly, MSD. A. Shimomura: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Research Grant: Eisai. E. Tokunaga: Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, AstraZeneca, Daiichi Sankyo. T. Mukohara: Financial Interests, Personal, Speaker’s Bureau: Eisai; Non-Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Sponsor/Funding: Eisai. Y. Naoi: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Research Grant: Eisai. S. Okumura, Y. Otake, D. Matsuoka, T. Takase, T. Semba: Financial Interests, Personal, Full or part-time Employment: Eisai Co., Ltd.. T. Suzuki: Financial Interests, Personal, Full or part-time Employment: Eisai Co., Ltd.; Financial Interests, Personal, Project Lead: Project Lead of E7389-LF in Eisai . H. Ishiguro: Financial Interests, Personal, Speaker’s Bureau: Eisai Co., Ltd.; Non-Financial Interests, Personal, Principal Investigator: Eisai Co., Ltd.; Financial Interests, Personal, Sponsor/Funding: Eisai Co., Ltd..