Study of GDC-0941 or GDC-0980 With Fulvestrant Versus Fulvestrant in Advanced or Metastatic Breast Cancer in Patients Resistant to Aromatase Inhibitor Therapy

• Progression-free survival (PFS) as assessed by the investigator per modified RECIST version 1.1 [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]
• Safety: incidence of adverse events [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]

• Objective tumor response as assessed by the investigator per modified RECIST v1.1 [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]
• Clinical benefit defined as partial response (PR), complete response (CR), or stable disease (SD) per modified RECIST v1.1 [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]
• Duration of confirmed objective response as assessed by the investigator per modified RECIST v1.1 [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]
• Proportion of patients with PIK3CA mutant tumors [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]
• Pharmacokinetic parameters of GDC-0941 and GDC-0980: time to maximum concentration [ Time Frame: Cycle 1, Day 15/16; Cycle 2, Day 15; Cycle, 6 Day 1 ] [ Designated as safety issue: No ]
• Pharmacokinetic parameters of GDC-0941 and GDC-0980: maximum concentration [ Time Frame: Cycle 1, Day 15/16; Cycle 2, Day 15; Cycle, 6 Day 1 ] [ Designated as safety issue: No ]
• Pharmacokinetic parameters of GDC-0941 and GDC-0980: Area under the concentration time curve [ Time Frame: Cycle 1, Day 15/16; Cycle 2, Day 15; Cycle, 6 Day 1 ] [ Designated as safety issue: No ]

• Objective tumor response as assessed by the investigator per modified RECIST v1.1 [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]
• Clinical benefit defined as partial response (PR), complete response (CR), or stable disease (SD) per modified RECIST v1.1 [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]
• Duration of confirmed objective response as assessed by the investigator per modified RECIST v1.1 [ Time Frame: until disease progression, up to 1 year ] [ Designated as safety issue: No ]

This is a multicenter, international, randomized, double-blinded, placebo-controlled, Phase II trial. Patients with advanced or Metastatic Breast Cancer (MBC) who have previously received treatment with an aromatase inhibitor. Patients will receive treatment with GDC-0941 + fulvestrant or GDC-0980 + fulvestrant or placebo + fulvestrant.

• Drug: fulvestrant
  Repeating intramuscular injection
• Drug: GDC-0941
  Repeating oral dose
• Drug: GDC-0980
  Repeating oral dose
• Drug: placebo
  Repeating oral dose

• Experimental: A
  Interventions:

  • Drug: fulvestrant
  • Drug: GDC-0941
• Experimental: B
  Interventions:

  • Drug: fulvestrant
  • Drug: GDC-0980
• Placebo Comparator: C
  Interventions:

  • Drug: fulvestrant
  • Drug: placebo
• Experimental: D
  Interventions:

  • Drug: fulvestrant
  • Drug: GDC-0941
• Placebo Comparator: E
  Interventions:

  • Drug: fulvestrant
  • Drug: placebo

Inclusion Criteria:

• Patients with ER-positive locally advanced breast cancer or Metastatic Breast Cancer (MBC). Postmenopausal women with locally advanced breast cancer or Metastatic Breast Cancer whose disease has progressed during or after treatment with an aromatase inhibitor. Part II: Postmenopausal women with locally advanced PIK3CA-mutant breast cancer or PIK3CA-mutant MBC that has progressed during or after treatment with an AI.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Patients must have measurable disease by RECIST v1.1 or bone-only disease
• Adequate hematologic and end-organ function
• Estrogen receptor-positive disease and HER2-negative disease

Exclusion Criteria:

• Prior treatment with fulvestrant, PI3K inhibitor, or mTOR inhibitor for advanced breast cancer or MBC
• Prior treatment with > one cytotoxic chemotherapy regimens or experienced recurrent or progressive disease on > two endocrine therapies for metastatic breast cancer
• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• History of clinically significant cardiac or pulmonary dysfunction
• Clinically significant history of liver disease
• Active uncontrolled autoimmune disease or active inflammatory disease
• Immunocompromised status
• Symptomatic hypercalcemia
• Need for current chronic corticosteroid therapy
• Pregnancy, lactation, or breastfeeding
• Known untreated or active central nervous system (CNS) metastases Other protocol-defined inclusion/exclusion criteria may apply.