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 (INAVO123)

Roche

Status and phase: Enrolling; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Placebo; Drug: Letrozole; Drug: Inavolisib; Drug: CDK4/6i

Study type: Interventional

Funder types: Industry

Identifiers

NCT06790693

WO45654

2024-516162-11-00 (Registry Identifier)

Details and patient eligibility

About

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).

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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450 participants in 2 patient groups, including a placebo group

Inavolisib + Letrozole + CDK4/6i

Experimental group

Description:

Participants will receive inavolisib, letrozole and CDK4/6i.

Treatment:

Drug: CDK4/6i

Drug: Letrozole

Drug: Inavolisib

Placebo + Letrozole + CDK4/6i

Placebo Comparator group

Description:

Participants will receive placebo, letrozole and CDK4/6i.

Treatment:

Drug: CDK4/6i

Drug: Letrozole

Drug: Placebo