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)
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
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:
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, depending on RP2D, as IV infusion on Day 1 and 8 of each 21-day cycle
Other Names:
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 as IV infusion on Day 1 and 8 of 21-day cycle
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase 1b: Recommended Phase 2 Dose (RP2D) of Eribulin Mesylate in Combination With PEGPH20 [Up to Cycle 28 (Cycle Length= 21 days)]
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.
- Phase 1b: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Eribulin Mesylate [Up to Cycle 28 (Cycle Length= 21 days)]
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.
Eligibility Criteria
Criteria
Inclusion Criteria
-
Metastatic Her-2- breast cancer
-
Up to 2 prior lines of cytotoxic or targeted anti-cancer therapy for metastatic disease
-
Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
Exclusion Criteria
-
Less than 6 months since prior neoadjuvant/adjuvant chemotherapy
-
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
-
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
-
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
-
Pregnant or breastfeeding
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Whittier | California | United States | 90602 | |
2 | Atlanta | Georgia | United States | 30318 | |
3 | Newnan | Georgia | United States | 30265 | |
4 | Anderson | Indiana | United States | 46011 | |
5 | Bethesda | Maryland | United States | 20817 | |
6 | Stony Brook | New York | United States | 11794 | |
7 | Kennewick | Washington | United States | 99336 |
Sponsors and Collaborators
- Eisai Inc.
- Halozyme Therapeutics
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- E7389-M000-219
- 2015-004740-19
Study Results
Participant Flow
Recruitment Details | Participants took part in the study at 4 investigative sites in the United States from 13 Jul 2016 to 16 Aug 2019. A total of 25 participants were screened and enrolled (signed informed consent form), of which 11 were screen failures, and 14 were treated. |
---|---|
Pre-assignment Detail | Study terminated early during Phase 1b Expansion Part and before initiating Phase 2 due to poor accrual. Data reported is based on initial dosing levels given to participants during Phase 1b. Combined data for participants who received Dose level 0 during determination of RP2D and confirmation of RP2D (Expansion Part) are reported as planned. |
Arm/Group Title | Phase 1b: Dose Level 1 | Phase 1b: Dose Level 0 and Expansion Part |
---|---|---|
Arm/Group Description | Participants received PEGylated recombinant human hyaluronidase (PEGPH20) 3.0 microgram per kilogram (mcg/kg), infusion, intravenously on Days -1 and 7 followed by eribulin mesylate 1.4 milligram per square meter (mg/m^2), infusion, intravenously, on Days 1 and 8 of each 21-day treatment cycle up to Cycle 28 (Dose level 1). | Participants received PEGPH20 1.6 mcg/kg, infusion, intravenously on Days -1 and 7 followed by eribulin mesylate 1.4 mg/m^2, infusion, intravenously, on Days 1 and 8 of each 21-day treatment cycle for up to Cycle 28 (Dose Level 0). After the determination of RP2D at this dosing level in Cycle 1 of Phase 1b, additional participants were enrolled in this dosing level for the confirmation of the RP2D in the Expansion Part for up to Cycle 28. |
Period Title: Overall Study | ||
STARTED | 5 | 9 |
COMPLETED | 3 | 7 |
NOT COMPLETED | 2 | 2 |
Baseline Characteristics
Arm/Group Title | Phase 1b: Dose Level 1 | Phase 1b: Dose Level 0 and Expansion Part | Total |
---|---|---|---|
Arm/Group Description | Participants received PEGPH20 3.0 mcg/kg, infusion, intravenously on Days -1 and 7 followed by eribulin mesylate 1.4 mg/m^2, infusion, intravenously, on Days 1 and 8 of each 21-day treatment cycle up to Cycle 28 (Dose level 1). | Participants received PEGPH20 1.6 mcg/kg, infusion, intravenously on Days -1 and 7 followed by eribulin mesylate 1.4 mg/m^2, infusion, intravenously, on Days 1 and 8 of each 21-day treatment cycle for up to Cycle 28 (Dose Level 0). After the determination of RP2D at this dosing level in Cycle 1 of Phase 1b, additional participants were enrolled in this dosing level for the confirmation of the RP2D in the Expansion Part for up to Cycle 28. | Total of all reporting groups |
Overall Participants | 5 | 9 | 14 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
55.2
(13.10)
|
52.8
(11.86)
|
53.6
(11.87)
|
Sex: Female, Male (Count of Participants) | |||
Female |
5
100%
|
9
100%
|
14
100%
|
Male |
0
0%
|
0
0%
|
0
0%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
0
0%
|
3
33.3%
|
3
21.4%
|
Not Hispanic or Latino |
5
100%
|
6
66.7%
|
11
78.6%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
3
60%
|
1
11.1%
|
4
28.6%
|
White |
2
40%
|
4
44.4%
|
6
42.9%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
4
44.4%
|
4
28.6%
|
Outcome Measures
Title | Phase 1b: Recommended Phase 2 Dose (RP2D) of Eribulin Mesylate in Combination With PEGPH20 |
---|---|
Description | 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. |
Time Frame | Up to Cycle 28 (Cycle Length= 21 days) |
Outcome Measure Data
Analysis Population Description |
---|
The safety analysis set included participants who received at least 1 dose of the study drug in Phase 1b. |
Arm/Group Title | Phase 1b, All Participants |
---|---|
Arm/Group Description | Participants received PEGPH20 3.0 mcg/kg or 1.6 mcg/kg, infusion, intravenously on Days -1 and 7 followed by eribulin mesylate 1.4 mg/m^2, infusion, intravenously, on Days 1 and 8 of first 21-day treatment cycle. After the determination of RP2D in Cycle 1 of Phase 1b, additional participants were enrolled for the confirmation of the RP2D in the Expansion Part for up to Cycle 28. |
Measure Participants | 14 |
Number [mg/m^2] |
NA
|
Title | Phase 1b: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Eribulin Mesylate |
---|---|
Description | 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. |
Time Frame | Up to Cycle 28 (Cycle Length= 21 days) |
Outcome Measure Data
Analysis Population Description |
---|
The safety analysis set included participants who received at least 1 dose of the study drug in Phase 1b. |
Arm/Group Title | Phase 1b, All Participants |
---|---|
Arm/Group Description | Participants received PEGPH20 3.0 mcg/kg or 1.6 mcg/kg, infusion, intravenously on Days -1 and 7 followed by eribulin mesylate 1.4 mg/m^2, infusion, intravenously, on Days 1 and 8 of first 21-day treatment cycle. After the determination of RP2D in Cycle 1 of Phase 1b, additional participants were enrolled for the confirmation of the RP2D in the Expansion Part for up to Cycle 28. |
Measure Participants | 14 |
Number [mcg/kg] |
NA
|
Adverse Events
Time Frame | From the first dose of study drug up to approximately 3 years 1 month | |||
---|---|---|---|---|
Adverse Event Reporting Description | Deaths that happened anytime during the study (including those during the treatment and after treatment discontinuation) are reported in this section. | |||
Arm/Group Title | Phase 1b: Dose Level 1 | Phase 1b: Dose Level 0 and Expansion Part | ||
Arm/Group Description | Participants received PEGPH20 3.0 mcg/kg, infusion, intravenously on Days -1 and 7 followed by eribulin mesylate 1.4 mg/m^2, infusion, intravenously, on Days 1 and 8 of each 21-day treatment cycle up to Cycle 28 (Dose level 1). | Participants received PEGPH20 1.6 mcg/kg, infusion, intravenously on Days -1 and 7 followed by eribulin mesylate 1.4 mg/m^2, infusion, intravenously, on Days 1 and 8 of each 21-day treatment cycle for up to Cycle 28 (Dose Level 0). After the determination of RP2D at this dosing level in Cycle 1 of Phase 1b, additional participants were enrolled in this dosing level for the confirmation of the RP2D in the Expansion Part for up to Cycle 28. | ||
All Cause Mortality |
||||
Phase 1b: Dose Level 1 | Phase 1b: Dose Level 0 and Expansion Part | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/5 (40%) | 3/9 (33.3%) | ||
Serious Adverse Events |
||||
Phase 1b: Dose Level 1 | Phase 1b: Dose Level 0 and Expansion Part | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/5 (20%) | 3/9 (33.3%) | ||
General disorders | ||||
Non-cardiac chest pain | 1/5 (20%) | 0/9 (0%) | ||
Injury, poisoning and procedural complications | ||||
Femur fracture | 0/5 (0%) | 1/9 (11.1%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Cancer pain | 0/5 (0%) | 1/9 (11.1%) | ||
Pericardial effusion malignant | 0/5 (0%) | 1/9 (11.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
Phase 1b: Dose Level 1 | Phase 1b: Dose Level 0 and Expansion Part | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/5 (100%) | 9/9 (100%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 1/5 (20%) | 2/9 (22.2%) | ||
Febrile neutropenia | 0/5 (0%) | 1/9 (11.1%) | ||
Lymphopenia | 0/5 (0%) | 1/9 (11.1%) | ||
Neutropenia | 1/5 (20%) | 5/9 (55.6%) | ||
Eye disorders | ||||
Vision blurred | 0/5 (0%) | 1/9 (11.1%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 0/5 (0%) | 3/9 (33.3%) | ||
Abdominal pain upper | 1/5 (20%) | 0/9 (0%) | ||
Constipation | 2/5 (40%) | 2/9 (22.2%) | ||
Diarrhoea | 1/5 (20%) | 1/9 (11.1%) | ||
Dyspepsia | 1/5 (20%) | 0/9 (0%) | ||
Flatulence | 1/5 (20%) | 0/9 (0%) | ||
Gastrooesophageal reflux disease | 1/5 (20%) | 0/9 (0%) | ||
Mouth ulceration | 0/5 (0%) | 1/9 (11.1%) | ||
Nausea | 2/5 (40%) | 1/9 (11.1%) | ||
Vomiting | 0/5 (0%) | 1/9 (11.1%) | ||
Abdominal distension | 0/5 (0%) | 1/9 (11.1%) | ||
General disorders | ||||
Catheter site inflammation | 0/5 (0%) | 1/9 (11.1%) | ||
Fatigue | 3/5 (60%) | 2/9 (22.2%) | ||
Nodule | 0/5 (0%) | 1/9 (11.1%) | ||
Oedema peripheral | 3/5 (60%) | 2/9 (22.2%) | ||
Pain | 0/5 (0%) | 2/9 (22.2%) | ||
Peripheral swelling | 2/5 (40%) | 1/9 (11.1%) | ||
Malaise | 0/5 (0%) | 1/9 (11.1%) | ||
Infections and infestations | ||||
Ear infection | 1/5 (20%) | 0/9 (0%) | ||
Nasopharyngitis | 0/5 (0%) | 1/9 (11.1%) | ||
Urinary tract infection | 1/5 (20%) | 1/9 (11.1%) | ||
Injury, poisoning and procedural complications | ||||
Scar | 0/5 (0%) | 1/9 (11.1%) | ||
Eye contusion | 0/5 (0%) | 1/9 (11.1%) | ||
Investigations | ||||
Blood lactic acid increased | 0/5 (0%) | 1/9 (11.1%) | ||
Neutrophil count decreased | 2/5 (40%) | 2/9 (22.2%) | ||
Weight decreased | 1/5 (20%) | 0/9 (0%) | ||
White blood cell count decreased | 1/5 (20%) | 2/9 (22.2%) | ||
Metabolism and nutrition disorders | ||||
Decreased appetite | 2/5 (40%) | 1/9 (11.1%) | ||
Diabetes mellitus | 0/5 (0%) | 1/9 (11.1%) | ||
Hyperglycaemia | 0/5 (0%) | 3/9 (33.3%) | ||
Hypokalaemia | 2/5 (40%) | 1/9 (11.1%) | ||
Hypomagnesaemia | 2/5 (40%) | 0/9 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 4/5 (80%) | 4/9 (44.4%) | ||
Back pain | 0/5 (0%) | 2/9 (22.2%) | ||
Bone pain | 2/5 (40%) | 1/9 (11.1%) | ||
Costochondritis | 0/5 (0%) | 1/9 (11.1%) | ||
Muscle spasms | 3/5 (60%) | 6/9 (66.7%) | ||
Musculoskeletal chest pain | 0/5 (0%) | 1/9 (11.1%) | ||
Musculoskeletal pain | 0/5 (0%) | 2/9 (22.2%) | ||
Myalgia | 1/5 (20%) | 2/9 (22.2%) | ||
Pain in extremity | 1/5 (20%) | 1/9 (11.1%) | ||
Neck pain | 0/5 (0%) | 1/9 (11.1%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Malignant neoplasm progression | 0/5 (0%) | 1/9 (11.1%) | ||
Malignant pleural effusion | 0/5 (0%) | 1/9 (11.1%) | ||
Nervous system disorders | ||||
Dizziness | 1/5 (20%) | 0/9 (0%) | ||
Dysgeusia | 0/5 (0%) | 1/9 (11.1%) | ||
Headache | 2/5 (40%) | 0/9 (0%) | ||
Neuropathy peripheral | 1/5 (20%) | 0/9 (0%) | ||
Neurotoxicity | 2/5 (40%) | 0/9 (0%) | ||
Peripheral sensory neuropathy | 0/5 (0%) | 1/9 (11.1%) | ||
Taste disorder | 0/5 (0%) | 1/9 (11.1%) | ||
Cognitive disorder | 0/5 (0%) | 1/9 (11.1%) | ||
Psychiatric disorders | ||||
Depression | 0/5 (0%) | 1/9 (11.1%) | ||
Renal and urinary disorders | ||||
Dysuria | 0/5 (0%) | 1/9 (11.1%) | ||
Nocturia | 0/5 (0%) | 1/9 (11.1%) | ||
Pollakiuria | 0/5 (0%) | 1/9 (11.1%) | ||
Polyuria | 0/5 (0%) | 1/9 (11.1%) | ||
Proteinuria | 0/5 (0%) | 1/9 (11.1%) | ||
Reproductive system and breast disorders | ||||
Breast pain | 0/5 (0%) | 1/9 (11.1%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 2/5 (40%) | 1/9 (11.1%) | ||
Dysphonia | 1/5 (20%) | 0/9 (0%) | ||
Dyspnoea | 2/5 (40%) | 0/9 (0%) | ||
Dyspnoea exertional | 0/5 (0%) | 1/9 (11.1%) | ||
Nasal congestion | 1/5 (20%) | 0/9 (0%) | ||
Oropharyngeal pain | 1/5 (20%) | 0/9 (0%) | ||
Pneumothorax | 0/5 (0%) | 1/9 (11.1%) | ||
Rhinorrhoea | 0/5 (0%) | 1/9 (11.1%) | ||
Upper-airway cough syndrome | 1/5 (20%) | 0/9 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Alopecia | 4/5 (80%) | 1/9 (11.1%) | ||
Palmar-plantar erythrodysaesthesia syndrome | 0/5 (0%) | 1/9 (11.1%) | ||
Scar pain | 0/5 (0%) | 1/9 (11.1%) | ||
Vascular disorders | ||||
Hot flush | 0/5 (0%) | 1/9 (11.1%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Eisai Medical Information |
---|---|
Organization | Eisai, Inc. |
Phone | 1-888-274-2378 |
esi_oncmedinfo@eisai.com |
- E7389-M000-219
- 2015-004740-19