A Study of Taselisib + Fulvestrant Versus Placebo + Fulvestrant in Participants With Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression During or After Aromatase Inhibitor Therapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Recurrence
Intervention: Taselisib; Placebo; Fulvestrant
Intervention description: Taselisib 4 mg was administered as two tablets of 2 mg each as per the schedule specified in the respective arm.; Placebo matching to taselisib was administered as per the schedule specified in the respective arm.; Fulvestrant 500 mg was administered as two IM injections of 250 mg each as per the schedule specified in the respective arms.
Intervention MeSH terms: Fulvestrant
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 631.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This international, multicenter, randomized, double-blinded, placebo-controlled study is
      designed to compare the efficacy and safety of taselisib + fulvestrant with that of placebo +
      fulvestrant in postmenopausal women with estrogen receptor (ER)-positive, human epidermal
      growth factor receptor-2 (HER2)-negative, oncogene that encodes for
      phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutant, unresectable, locally
      advanced or metastatic breast cancer after recurrence or progression during or after an
      aromatase inhibitor (AI) therapy. There will be a 2:1 randomization to the taselisib arm
      versus the placebo arm. Enrollment will be enriched for participants with PIK3CA mutant
      tumors via central testing. The anticipated duration of the study is approximately 3.5 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Postmenopausal women with histologically or cytologically confirmed locally advanced
             or metastatic estrogen receptor (ER) positive breast cancer

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Participants for whom endocrine therapy (example [e.g.], fulvestrant) is recommended
             and treatment with cytotoxic chemotherapy is not indicated at time of entry into the
             study

          -  Radiologic/objective evidence of recurrence or progression to the most recent systemic
             therapy for breast cancer

          -  Radiologic/objective evidence of breast cancer recurrence or progression while on or
             within 12 months of the end of adjuvant treatment with an aromatase inhibitor (AI), or
             progression while on or within 1 month of the end of prior AI treatment for locally
             advanced or metastatic breast cancer

          -  Measurable disease via Response Evaluation Criteria in Solid Tumors (RECIST) Version
             1.1 (v1.1) or non-measurable, evaluable disease with at least one evaluable bone
             lesion via RECIST v1.1

          -  Consent to provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block
             (preferred) or a minimum of 20 (25 preferred) freshly cut unstained tumor slides from
             the most recently collected, available tumor tissue for oncogene that encodes for
             phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutation testing

          -  A valid cobas PIK3CA mutation result by central testing is required

          -  Adequate hematologic and end-organ function within 28 days prior to treatment
             initiation

        Exclusion Criteria:

          -  Human epidermal growth factor receptor 2 (HER2)-positive disease by local laboratory
             testing (immunohistochemistry 3 positive [IHC 3+] staining or in situ hybridization
             positive)

          -  Prior treatment with fulvestrant

          -  Prior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor, mammalian
             target of rapamycin (mTOR) inhibitor (e.g. everolimus), or protein kinase B (AKT)
             inhibitor

          -  Prior anti-cancer therapy within 2 weeks prior to Day 1 of Cycle 1

          -  Prior radiation therapy within 2 weeks prior to Day 1 of Cycle 1

          -  All acute treatment-related toxicity must have resolved to Grade less than or equal to
             (</=) 1 or be deemed stable by the Investigator

          -  Prior treatment with greater than (>) 1 cytotoxic chemotherapy regimen for metastatic
             breast cancer

          -  Concurrent hormone replacement therapy

          -  Known untreated or active central nervous system (CNS) metastases

          -  Type 1 or Type 2 diabetes mellitus requiring anti-hyperglycemic medications

          -  History of inflammatory bowel disease or active bowel inflammation

          -  Clinically significant cardiac or pulmonary dysfunction

          -  Clinically significant history of liver disease, including cirrhosis, current alcohol
             abuse, or current known active infection with human immunodeficiency virus (HIV),
             hepatitis B or C virus