Metastatic Breast Cancer
Conditions
Keywords
PEGylated Recombinant Human Hyaluronidase, Eribulin Mesylate, E7389, PEGPH20, Human Epidermal Growth Factor Receptor 2-Negative, High-Hyaluronan
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.
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).
Interventions
DRUGEribulin 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
OTHERBiologic: 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
OTHERBiologic: 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
Sponsors
Halozyme Therapeutics
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b: Dose Level 1 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). | 5 |
| Phase 1b: Dose Level 0 and Expansion Part 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. | 9 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Sponsor termination | 2 | 2 |
Baseline characteristics
| Characteristic | Phase 1b: Dose Level 0 and Expansion Part | Total | Phase 1b: Dose Level 1 |
|---|---|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 11.86 | 53.6 years STANDARD_DEVIATION 11.87 | 55.2 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 11 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Female | 9 Participants | 14 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 5 | 3 / 9 |
| other Total, other adverse events | 5 / 5 | 9 / 9 |
| serious Total, serious adverse events | 1 / 5 | 3 / 9 |
Outcome results
Primary
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.
Time frame: Up to Cycle 28 (Cycle Length= 21 days)
Population: The safety analysis set included participants who received at least 1 dose of the study drug in Phase 1b.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b, All Participants | Phase 1b: Recommended Phase 2 Dose (RP2D) of Eribulin Mesylate in Combination With PEGPH20 | NA mg/m^2 |
Primary
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.
Time frame: Up to Cycle 28 (Cycle Length= 21 days)
Population: The safety analysis set included participants who received at least 1 dose of the study drug in Phase 1b.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b, All Participants | Phase 1b: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Eribulin Mesylate | NA mcg/kg |