Study of Eribulin Mesylate in Combination With PEGylated Recombinant Human Hyaluronidase (PEGPH20) Versus Eribulin Mesylate Alone in Subjects With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, High-Hyaluronan (HA) Metastatic Breast Cancer (MBC)

A Randomized, Open-label, Multicenter, Phase 1b/2 Study of Eribulin Mesylate in Combination With PEGylated Recombinant Human Hyaluronidase (PEGPH20) Versus Eribulin Mesylate Alone in Subjects With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, High-Hyaluronan (HA) Metastatic Breast Cancer (MBC)

The primary objective for the study is as follows:

For the Phase 1b - to determine safety tolerability and recommended Phase 2 dose (RP2D) of eribulin mesylate in combination with PEGylated recombinant human hyaluronidase (PEGPH20) in participants with Human Epidermal Growth Factor Receptor (HER2)-negative metastatic breast cancer (MBC) previously treated with up to two lines of systemic anticancer therapy in the metastatic setting.

For the Phase 2 - to evaluate objective response rate (ORR) of eribulin mesylate in combination with PEGPH20 in participants with HER2-negative, High-Hyaluronan (HA)-high, MBC previously treated with up to 2 lines of systemic anticancer therapy in the metastatic setting.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Eribulin mesylate; Drug: Eribulin mesylate; Drug: Eribulin mesylate; Other: Biologic: PEGylated recombinant human hyaluronidase (PEGPH20); Other: Biologic: PEGylated recombinant human hyaluronidase

Detailed Description

Phase 1b will occur in two parts:

Part 1: Run-in safety cohort(s) (dose levels 1, 0, and -1, as necessary) of 6 participants each will be conducted until the RP2D is determined. The purpose of the run-in safety cohort(s) is to study the safety of the 2-drug combination and determine a RP2D. Dose limiting toxicity (DLT) will be assessed in the first cycle to determine the RP2D of eribulin mesylate in combination with PEGPH20.

Part 2 (Phase 1b "Expansion Part"): A total of 12 additional participants will be enrolled at the RP2D determined in Part 1 (using Phase 1b criteria, i.e., participants previously treated with up to 2 lines of systemic anticancer therapy) in order to assess the safety profile of the combination and identify any potential safety signals and the incidence of thromboembolic events in this population (RP2D determined dosing).

In Phase 2, participants will be stratified by triple negative breast cancer (TNBC) status and randomized 1:1 to receive eribulin mesylate and PEGPH20 at the established RP2D level or eribulin mesylate alone at 1.4 milligrams per square meters (mg/m^2).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Whittier, California, United States, 90602
  • Georgia
    • Atlanta, Georgia, United States, 30318
    • Newnan, Georgia, United States, 30265
  • Indiana
    • Anderson, Indiana, United States, 46011
  • Maryland
    • Bethesda, Maryland, United States, 20817
  • New York
    • Stony Brook, New York, United States, 11794
  • Washington
    • Kennewick, Washington, United States, 99336

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Metastatic Her-2- breast cancer
2. Up to 2 prior lines of cytotoxic or targeted anti-cancer therapy for metastatic disease
3. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

Exclusion Criteria

1. Less than 6 months since prior neoadjuvant/adjuvant chemotherapy
2. Known central nervous system (CNS) disease, except for those participants with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period
3. Previous history or current evidence of deep vein thrombosis (DVT), hereditary thrombophilic syndromes, pulmonary embolism (PE), cerebral vascular accident (CVA), transient ischemic attack (TIA), atrial fibrillation (AF), or active carotid artery disease requiring treatment
4. Treatment with chemotherapy, hormonal, or biological therapy within the previous 3 weeks, radiation or small molecule targeted therapy within the previous 2 weeks preceding informed consent
5. Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eribulin mesylate plus PEGPH20 (Phase 1b); Recommended Phase 2 dose (RP2D) will be determined from the below dose levels: Dose level 1: PEGPH20 (3.0 microgram per kilogram (mcg/kg)) followed by eribulin mesylate (1.4 milligrams per square meter (mg/m^2)) or; Dose level 0: PEGPH20 (1.6 mcg/kg) followed by eribulin mesylate (1.4 mg/m^2) or; Dose level -1: PEGPH20 (1.6 mcg/kg) followed by eribulin mesylate (1.1 mg/m^2) Dose level 1 can be selected as the RP2D if no more than 1 out of 6 participants has a DLT; DLT was only observed from the first treatment cycle; otherwise, Dose level 0 will be assessed in a second cohort of 6 subjects and will be selected as the RP2D if no more than 1 subject has a DLT. Otherwise, Dose level - 1 will be assessed in a third cohort of 6 subjects. Upon determination of the RP2D, study Phase 1b Expansion Part will proceed to confirm the RP2D, and thereafter Phase 2 part will proceed.	Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 or 1.1 mg/m^2 as intravenous (IV) infusion on Day 1 and 8 of 21-day cycle; Other Names: E7389; Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 or 1.1 mg/m^2, depending on RP2D, as IV infusion on Day 1 and 8 of each 21-day cycle; Other Names: E7389; Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 as IV infusion on Day 1 and 8 of 21-day cycle; Other Names: E7389; Other: Biologic: PEGylated recombinant human hyaluronidase (PEGPH20); PEGPH20 will be administered at 3.0 mcg/kg or 1.6 mcg/kg as IV infusion on Day -1 and 7 of 21-day cycle
Experimental: Eribulin mesylate plus PEGPH20 (Phase 2); Participants will receive eribulin mesylate and PEGPH20 at the established RP2D level achieved in the Phase 1b.	Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 or 1.1 mg/m^2 as intravenous (IV) infusion on Day 1 and 8 of 21-day cycle; Other Names: E7389; Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 or 1.1 mg/m^2, depending on RP2D, as IV infusion on Day 1 and 8 of each 21-day cycle; Other Names: E7389; Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 as IV infusion on Day 1 and 8 of 21-day cycle; Other Names: E7389; Other: Biologic: PEGylated recombinant human hyaluronidase; PEGPH20 will be administered at 3.0 mcg/kg or 1.6 mcg/kg, depending on RP2D, as IV infusion on Day -1 and 7 of each 21-day cycle
Experimental: Eribulin mesylate (Phase 2); Participants will receive eribulin mesylate at 1.4 mg/m^2.	Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 or 1.1 mg/m^2 as intravenous (IV) infusion on Day 1 and 8 of 21-day cycle; Other Names: E7389; Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 or 1.1 mg/m^2, depending on RP2D, as IV infusion on Day 1 and 8 of each 21-day cycle; Other Names: E7389; Drug: Eribulin mesylate; Eribulin mesylate will be administered at 1.4 mg/m^2 as IV infusion on Day 1 and 8 of 21-day cycle; Other Names: E7389

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Recommended Phase 2 Dose (RP2D) of Eribulin Mesylate in Combination With PEGPH20	The RP2D was the maximum tolerated dose (MTD) or less. The MTD was determined as the dose level (1, 0) at which less than or equal to (<=) 1 of 6 evaluable participants experienced dose limiting toxicity (DLT) within the first 21 days of treatment (end of Cycle 1). Upon determination of RP2D in Cycle 1 of Phase 1b, RP2D was to be confirmed in Phase 1b-expansion Part.	Up to Cycle 28 (Cycle Length= 21 days)
Phase 1b: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Eribulin Mesylate	The RP2D was the MTD or less. The MTD was determined as the dose level (1, 0) at which <=1 of 6 evaluable participants experienced DLT within the first 21 days of treatment (end of Cycle 1). Upon determination of RP2D in Cycle 1 of Phase 1b, RP2D was to be confirmed in Phase 1b-expansion Part.	Up to Cycle 28 (Cycle Length= 21 days)

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Collaborators: Halozyme Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2016
• Primary Completion (Actual): August 16, 2019
• Study Completion (Actual): August 16, 2019

Study Registration Dates

• First Submitted: April 26, 2016
• First Submitted That Met QC Criteria: April 27, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): July 13, 2020
• Last Update Submitted That Met QC Criteria: June 25, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Eribulin Mesylate; E7389; PEGPH20; Human Epidermal Growth Factor Receptor 2-Negative; PEGylated Recombinant Human Hyaluronidase; High-Hyaluronan
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: E7389-M000-219; 2015-004740-19 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No