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

ID#: NCT06790693

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 3

Recruitment Status: Recruiting

Start Date: April 09, 2025

End Date: May 30, 2032

Contact Information:
Reference Study ID Number
888-662-6728 (U.S. Only)
Summary: 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).
Eligibility:

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