A Study of GDC-0810 Versus Fulvestrant in Postmenopausal Women With Advanced or Metastatic Breast Cancer Resistant to Aromatase Inhibitor (AI) Therapy

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, Open-Label, Randomized Study of GDC-0810 Versus Fulvestrant in Postmenopausal Women With Advanced or Metastatic ER+ /HER2- Breast Cancer Resistant to Aromatase Inhibitor Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Fulvestrant
* Drug: GDC-0810


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fulvestrant<br>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. | Drug: Fulvestrant<br>* 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.<br>|
| Experimental: GDC-0810<br>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. | Drug: GDC-0810<br>* GDC-0810 will be administered as tablets at a dose of 600 mg orally once daily.<br>* Other names: RO7056118;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | 
| 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. | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death from any cause. | From Day 1 to death from any cause, 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 | 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. | From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | 
| 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. | From objective response to PD or death from any cause, assessed up to end of study (up to approximately 25 months) | 
| 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) | 
| 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) | 
| 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) | Predose (within 30 minutes of GDC-0810 administration) and 3 hours postdose on Day 1 of Cycles 1 and 3; Cycle length=28 days |