Inclusion Criteria:
- Women or men aged =>18 years with histologically documented triple-negative breast
cancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced or
metastatic and is not amenable to resection with curative intent
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Adequate hematologic and organ function within 14 days prior to treatment initiation
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1
- Consent to submit a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or
freshly cut unstained, serial tumor slides from the most recently collected tumor
tissue for central molecular analysis:
- Valid results from central molecular analysis confirming PIK3CA/AKT1/PTEN-altered
status in tumor tissue by next-generation sequencing (NGS)
Exclusion Criteria:
- Treatment with approved or investigational cancer therapy within 14 days prior to
treatment initiation
- Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or
HR+/HER2- adenocarcinoma of the breast
- Participants with HR+/HER2- breast cancer for whom endocrine-based therapy is
considered an appropriate option per local clinical guidelines (i.e. participants
should not be considered eligible for endocrine-based treatment)
- History of or known presence of brain or spinal cord metastases
- Malignancies other than breast cancer within 5 years prior to treatment initiation
(except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin
carcinoma, or Stage I uterine cancer)
- Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)
- History of malabsorption syndrome or other condition that would interfere with enteral
absorption or results in the inability or unwillingness to swallow pills
- Active infection requiring antibiotics
- Known human immunodeficiency virus (HIV) infection
- Known clinically significant history of liver disease consistent with Child-Pugh Class
B or C, including active viral or other hepatitis, current drug or alcohol abuse, or
cirrhosis
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to initiation of treatment (or anticipated need during study)
- Pregnant or breastfeeding, or intending to become pregnant during the study
- Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart
failure, left ventricular ejection fraction [LVEF] <50%, active ventricular arrhythmia
requiring medication, history of myocardial infarction within 6 months of treatment
initiation, clinically significant electrocardiogram [ECG] abnormalities).
- Need for chronic corticosteroid therapy of >=10 mg of prednisone per day or an
equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a
chronic disease
- Unresolved, clinically significant toxicity from prior therapy
- Uncontrolled clinical symptoms including pleural effusion, pericardial effusion, or
ascites, tumor-related pain, hypercalcemia (or symptomatic hypercalcemia requiring
continued use of bisphosphonate therapy)
- History of Type I or Type II diabetes mellitus requiring insulin
- Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
- History of or active inflammatory bowel disease or active bowel inflammation
- Clinically significant lung disease (including pneumonitis, interstitial lung disease,
idiopathic pulmonary fibrosis, cystic fibrosis, active infection/ history of
opportunistic infections)
- Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5
drug-elimination half-lives, whichever is longer, prior to initiation of treatment
- Grade >=2 peripheral neuropathy