Breast Cancer
Conditions
Brief summary
The primary purpose of this study is to evaluate the efficacy, safety, and tolerability of GDC-0810 compared with fulvestrant in postmenopausal women with advanced or metastatic estrogen receptor positive (ER+)/ human epidermal growth factor receptor 2 negative (HER2-) breast cancer resistant to AI therapy. The development of GDC-0810 has been halted by the Sponsor and the enrollment in this study has been discontinued. Participants currently enrolled in the study who are experiencing clinical benefit may continue receiving GDC-0810 as a single agent or fulvestrant until disease progression (PD), unmanageable toxicity, withdrawal of consent, exhaustion of GDC-0810 drug supply, or termination of the study by the Sponsor.
Interventions
DRUGFulvestrant
Fulvestrant at a dose of 500 mg as two intramuscular injections will be administered on Day 1 and Day 15 of Cycle 1, and on Day 1 of each subsequent 28-day cycle.
DRUGGDC-0810
GDC-0810 will be administered as tablets at a dose of 600 mg orally once daily.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women with histologically or cytologically confirmed invasive, ER+/HER- (defined by local guidelines) metastatic or inoperable, locally advance breast cancer * Participants for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study * Participants must have measurable disease by RECIST v1.1 or non-measurable, evaluable disease with atleast one evaluable bone lesion by RECIST v1.1 based on radiologic scans within 28 days of Day 1 of Cycle 1 * Participants with radiologic/objective evidence of breast cancer recurrence or progression while on or within 6 months after the end of adjuvant treatment with an AI, or progression while on or within 1 month after the end of prior AI treatment for locally advanced or metastatic breast cancer
Exclusion criteria
* HER2-positive disease * Prior treatment with fulvestrant * Prior treatment with greater than (\>) 1 cytotoxic chemotherapy regimen or \>2 endocrine therapies for advanced or metastatic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Intent-to-Treat (ITT) Population | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1 or death on study from any cause. |
| PFS According to RECIST v1.1 in Participants With Estrogen Receptor (ESR)1 Mutations | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1 or death on study from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) Assessed Using RECIST v1.1 | From objective response to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | DOR was defined as the time from first observation of an objective response until first observation of disease progression as assessed by the investigator according to RECIST v1.1 or death from any cause. |
| Percentage of Participants With Clinical Benefit (PR, CR, or Stable Disease, Lasting for At Least 24 Weeks) Assessed Using RECIST v1.1 | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | — |
| Overall Survival (OS) | From Day 1 to death from any cause, assessed up to end of study (up to approximately 25 months) | OS is defined as the time from randomization to death from any cause. |
| GDC-0810 Plasma Concentrations by Visit | Predose (within 30 minutes of GDC-0810 administration) and 3 hours postdose on Day 1 of Cycles 1 and 3; Cycle length=28 days | Concentration of GDC-0810 measured in plasma after a single dose (Cycle 1 Day 1) and at steady state (Cycle 3 Day 1) |
| Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | From Day 1 to 28 days after last dose of study drug, assessed up to end of study (up to approximately 25 months) | — |
| Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]) According to RECIST v1.1 | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | Objective Response was defined as the percentage of participants who attained CR or PR. CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. |
Countries
Australia, Germany, South Korea, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GDC-0810 Participants will receive three 200 mg tablets (total dose = 600 mg) of GDC-0810 orally once daily until disease progression, unmanageable toxicity, withdrawal of consent, exhaustion of GDC-0810 drug supply, or termination of study by the Sponsor. | 36 |
| Fulvestrant Participants will receive 500 milligrams (mg) of fulvestrant as two intramuscular injections (250 mg each) on Day 1 and Day 15 of Cycle 1, and on Day 1 of each subsequent 28-day cycle until disease progression, unmanageable toxicity, withdrawal of consent, exhaustion of GDC-0810 drug supply, or termination of study by the Sponsor. | 35 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 12 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Progressive Disease | 2 | 7 |
| Overall Study | Sponsor Decision | 13 | 14 |
| Overall Study | Withdrawal by Subject | 9 | 9 |
Baseline characteristics
| Characteristic | Fulvestrant | Total | GDC-0810 |
|---|---|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 10.5 | 63.2 years STANDARD_DEVIATION 11.7 | 62.2 years STANDARD_DEVIATION 12.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 28 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 40 Participants | 22 Participants |
| Sex: Female, Male Female | 35 Participants | 71 Participants | 36 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 | 12 / 35 | 4 / 35 |
| other Total, other adverse events | 33 / 35 | 31 / 35 |
| serious Total, serious adverse events | 7 / 35 | 5 / 35 |
Outcome results
Primary
PFS According to RECIST v1.1 in Participants With Estrogen Receptor (ESR)1 Mutations
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1 or death on study from any cause.
Time frame: From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
Population: Outcome Measures not assessed based on pre-specified thresholds not having been met.
Primary
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Intent-to-Treat (ITT) Population
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1 or death on study from any cause.
Time frame: From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
Population: Outcome Measures not assessed based on pre-specified thresholds not having been met.
Secondary
Duration of Response (DOR) Assessed Using RECIST v1.1
DOR was defined as the time from first observation of an objective response until first observation of disease progression as assessed by the investigator according to RECIST v1.1 or death from any cause.
Time frame: From objective response to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
Population: Outcome Measures not assessed based on pre-specified thresholds not having been met.
Secondary
GDC-0810 Plasma Concentrations by Visit
Concentration of GDC-0810 measured in plasma after a single dose (Cycle 1 Day 1) and at steady state (Cycle 3 Day 1)
Time frame: Predose (within 30 minutes of GDC-0810 administration) and 3 hours postdose on Day 1 of Cycles 1 and 3; Cycle length=28 days
Population: Participants who received at least one dose of any study drug and provided a post-dose blood sample in the GDC-0810 arm
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-0810 | GDC-0810 Plasma Concentrations by Visit | Cycle 1, Day 1 (3 hours post-dose) | 6510 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 574 |
| GDC-0810 | GDC-0810 Plasma Concentrations by Visit | Cycle 3, Day 1 (pre-dose) | 528 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 266 |
| GDC-0810 | GDC-0810 Plasma Concentrations by Visit | Cycle 3, Day 1 (3 hours post-dose) | 10100 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 132 |
Secondary
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause.
Time frame: From Day 1 to death from any cause, assessed up to end of study (up to approximately 25 months)
Population: Outcome Measures not assessed based on pre-specified thresholds not having been met.
Secondary
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Time frame: From Day 1 to 28 days after last dose of study drug, assessed up to end of study (up to approximately 25 months)
Population: Participants who received at least one dose of any study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GDC-0810 | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 97.1 percentage of participants |
| GDC-0810 | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 20.0 percentage of participants |
| Fulvestrant | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 91.4 percentage of participants |
| Fulvestrant | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 14.3 percentage of participants |
Secondary
Percentage of Participants With Clinical Benefit (PR, CR, or Stable Disease, Lasting for At Least 24 Weeks) Assessed Using RECIST v1.1
Time frame: From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GDC-0810 | Percentage of Participants With Clinical Benefit (PR, CR, or Stable Disease, Lasting for At Least 24 Weeks) Assessed Using RECIST v1.1 | 16.7 percentage of participants |
| Fulvestrant | Percentage of Participants With Clinical Benefit (PR, CR, or Stable Disease, Lasting for At Least 24 Weeks) Assessed Using RECIST v1.1 | 31.4 percentage of participants |
Secondary
Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]) According to RECIST v1.1
Objective Response was defined as the percentage of participants who attained CR or PR. CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GDC-0810 | Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]) According to RECIST v1.1 | 0 percentage |
| Fulvestrant | Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]) According to RECIST v1.1 | 8.6 percentage |