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A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer

Trial Status: Active

This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in patients with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

Inclusion Criteria

  • Confirmed diagnosis of HR+/HER2- breast cancer
  • Metastatic or locally advanced disease not amenable to curative therapy
  • Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
  • Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal
  • Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
  • Consent to provide fresh or archival tumor tissue specimen
  • Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1; "bone-only" disease, even if considered measurable, is not eligible
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Life expectancy of > 6 months
  • Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria

  • Metaplastic breast cancer
  • Any history of leptomeningeal disease or carcinomatous meningitis
  • Any prior systemic therapy for metastatic breast cancer
  • Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
  • Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
  • Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
  • Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases are eligible
  • Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period
  • Symptomatic active lung disease, or requiring daily supplemental oxygen
  • History of inflammatory bowel disease or active bowel inflammation
  • Anti-cancer therapy within 2 weeks before study entry
  • Investigational drug(s) within 4 weeks before randomization
  • Prior radiotherapy to >= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation
  • Chronic corticosteroid therapy or immunosuppressants
  • Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of study treatment
  • Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1


Emory University Hospital / Winship Cancer Institute


Massachusetts General Hospital Cancer Center
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Komal Jhaveri
Phone: 646-888-5157
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE

North Carolina

Wake Forest University Health Sciences
Status: ACTIVE

Trial Phase Phase II/III

Trial Type Treatment

Lead Organization
Hoffmann-La Roche

  • Primary ID WO41554
  • Secondary IDs NCI-2020-02312, 2019-002455-42
  • ID NCT04191499