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

Phase 3

Not yet recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Inavolisib; Drug: Placebo; Drug: CDK4/6i; Drug: Letrozole

• Registration Number: NCT06790693
• Lead Sponsor: Hoffmann-La Roche

Brief 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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-14
• Study First Submitted QC: 2025-01-22
• Last Update Submitted: 2025-01-22
• Study First Posted: 2025-01-24
• Last Update Posted: 2025-01-24
• Study Start: 2025-02-28
• Primary Completion: 2028-01-29
• Study Completion: 2032-05-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 450

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inavolisib + Letrozole + CDK4/6i	Inavolisib	Participants will receive inavolisib, letrozole and CDK4/6i.
Inavolisib + Letrozole + CDK4/6i	CDK4/6i	Participants will receive inavolisib, letrozole and CDK4/6i.
Inavolisib + Letrozole + CDK4/6i	Letrozole	Participants will receive inavolisib, letrozole and CDK4/6i.
Placebo + Letrozole + CDK4/6i	Placebo	Participants will receive placebo, letrozole and CDK4/6i.
Placebo + Letrozole + CDK4/6i	CDK4/6i	Participants will receive placebo, letrozole and CDK4/6i.
Placebo + Letrozole + CDK4/6i	Letrozole	Participants will receive placebo, letrozole and CDK4/6i.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years)

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From randomization to death from any cause (up to 7 years)
Investigator-assessed Objective Response Rate (ORR)	Up to 7 years
Investigator-assessed Duration of Response (DOR)	From the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years)
Investigator-assessed Clinical Benefit Rate (CBR)	Up to 7 years
Time to Confirmed Deterioration (TTCD) in Pain	From baseline until end of follow-up (up to 7 years)
TTCD in Physical Function	From baseline until end of follow-up (up to 7 years)
TTCD in Role Function	From baseline until end of follow-up (up to 7 years)
TTCD in Global Health Status	From baseline until end of follow-up (up to 7 years)
Percentage of Participants with Adverse Events	From baseline until end of follow-up (up to 7 years)
Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)	Up to 7 years
Number of Participants Reporting Each Response Option for Treatment Side-effect Bother Single-item General Population, Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General Questionnaire; (FACT-G)	Up to 7 years
Change from Baseline in Symptomatic Treatment Toxicities as Assessed Through use of the PRO-CTCAE	Baseline up to 7 years
Change from Baseline in Treatment Side-effect Bother as Assessed Through use of the FACT-G GP5 Item	Baseline up to 7 years