A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer

Purpose

This study will evaluate the efficacy and safety of the combination of inavolisib plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer (ABC).

Condition

  • Breast Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Women or men with histologically or cytologically confirmed carcinoma of the breast - Documented ER-positive and/or progesterone receptor-positive tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines - Documented HER2-negative tumor according to ASCO/CAP guidelines - De-novo HR+ , HER2- ABC, or, alternatively, relapsed HR+ , HER2- ABC after at least 2 years of standard neoadjuvant/adjuvant endocrine therapy without disease progression during that treatment and disease-free interval of at least 1 year since the completion of that treatment - Participants who have bilateral breast cancers which are both HR-positive and HER2-negative - Confirmation of biomarker eligibility - Consent to provide fresh or archival tumor tissue specimen - Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria

  • Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required - Metaplastic breast cancer - Any prior systemic therapy for locally advanced unresectable or metastatic breast cancer - Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes - Any history of leptomeningeal disease or carcinomatous meningitis - Known and untreated, or active CNS metastases. Participants with a history of treated CNS metastases are eligible - Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye - Symptomatic active lung disease - History of or active inflammatory bowel disease - Any active bowel inflammation - Prior hematopoietic stem cell or bone marrow transplantation - Treatment with strong cytochrome P450 (CYP) 3A4 inhibitors or strong CYP3A4 inducers within 4 weeks or 5 drug-elimination half-lives, prior to initiation of study treatment

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Inavolisib + Letrozole + CDK4/6i
Participants will receive inavolisib, letrozole and CDK4/6i.
  • Drug: Inavolisib
    Participants will receive oral inavolisib once daily (QD).
    Other names:
    • GDC-0077
    • Itovebi
  • Drug: CDK4/6i
    Participants will receive CDK4/6i on either Days 1-21 or Days 1-28 of each 28-day cycle.
  • Drug: Letrozole
    Participants will receive oral letrozole QD.
Placebo Comparator
Placebo + Letrozole + CDK4/6i
Participants will receive placebo, letrozole and CDK4/6i.
  • Drug: Placebo
    Participants will receive oral placebo QD.
  • Drug: CDK4/6i
    Participants will receive CDK4/6i on either Days 1-21 or Days 1-28 of each 28-day cycle.
  • Drug: Letrozole
    Participants will receive oral letrozole QD.

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37204

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: WO45654 https://forpatients.roche.com/
888-662-6728 (U.S. Only)
global-roche-genentech-trials@gene.com