Phase 1 multicenter, open-label study to establish the maximum tolerated dose (MTD) of two administration schedules of E7389 (eribulin) liposomal formulation in patients (pts) with solid tumors.

IH Zubairi, Emma Dean, LR Molife, JS Lopez, M Ranson, F El-Khouly, CI Savulsky, L Reyderman, Y Jia, E Hutton, R Morrison, L Sweeting, A Greystoke, J Barriuso, RS Kristeleit, TRJ Evans

    Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

    Abstract

    Background: Eribulin, a microtubule dynamics inhibitor, is approved in the US for the treatment of pts with metastatic breast cancer who have previously received ≥ 2 chemotherapeutic regimens for metastatic disease including an anthracycline and a taxane in the adjuvant/metastatic setting. Preclinical evidence suggested improved efficacy and lower toxicity with a liposomal formulation of eribulin (eribulin-LF). The primary objective of this study was to determine the MTD and dosing schedule for eribulin-LF. Secondary objectives included determining safety, pharmacokinetics (PK), and efficacy. Methods: Using a conventional 3 + 3 study design, eligible pts received escalating doses (1.0 to 3.5 mg/m2) of eribulin-LF (60-min, i.v. infusion) on day (D) 1 of a 21-day cycle (schedule [S] 1) or on D1 and D15 of a 28-day cycle (S2). An expansion phase confirmed the safety of eribulin-LF in pts with endometrial, ovarian, or HER2-negative breast cancer. Results: Of 58 pts (S1: n = 20; S2: n = 38): 65% were female, median age was 62 yrs (range 33–75), 65% had an ECOG PS of 1, and 10 pts had metastatic breast cancer. Dose-limiting toxicities were: S1, grade (G) 4 hypophosphatemia (n = 1), G4 increased ALT/AST (n = 1), both at eribulin-LF 1.5 mg/m2; S2, G4 febrile neutropenia (n = 1; 1.5 mg/m2); G3 increased ALT/AST (n = 1), and G4 neutropenia (n = 1), both at 2 mg/m2. MTD was 1.4 mg/m2 in S1 and 1.5 mg/m2in S2; the latter dose and schedule were used in the expansion phase (n = 23). Treatment-emergent adverse events (TEAEs) included peripheral neuropathy (S1: 35%, S2: 8%) and neutropenia (S1: 20%, S2: 34%). TEAEs of G3 or higher occurred in 55% (S1) and 39% (S2). Eribulin-LF exhibited single-phase PK, and was quantifiable ~18 days postdose. Exposure was dose-dependent and t1/2 was ~35 hrs. Promising clinical activity was observed in pts with breast cancer (5/10 partial responses, 3/10 stable disease). Conclusions: In this phase 1 study, eribulin-LF was well tolerated, with promising activity in patients with breast cancer. Eisai Inc. Clinical trial information: NCT01945710
    Original languageEnglish
    Title of host publicationJournal of Clinical Oncology
    Volume34
    Edition15_suppl abstr 2524
    Publication statusPublished - 2016
    EventASCO annual conference 2016 - Chicago, United States
    Duration: 3 Jun 20167 Jun 2016

    Conference

    ConferenceASCO annual conference 2016
    Country/TerritoryUnited States
    CityChicago
    Period3/06/167/06/16

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