RecruitingInterventionalPhase 3

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus a CDK4/6 Inhibitor and Letrozole Versus Placebo Plus a CDK4/6 Inhibitor and Letrozole in Patients With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer

NCT ID: NCT06790693Sponsor: Hoffmann-La RocheLast updated: 2026-06-03

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).

Arms & interventions

DrugInavolisib
Participants will receive oral inavolisib once daily (QD).
DrugPlacebo
Participants will receive oral placebo QD.
DrugCDK4/6i
Participants will receive CDK4/6i on either Days 1-21 or Days 1-28 of each 28-day cycle.
DrugLetrozole
Participants will receive oral letrozole QD.

Outcome measures

Primary

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

Secondary

Overall Survival (OS)
Time frame: From randomization to death from any cause (up to 7 years)
Investigator-assessed Objective Response Rate (ORR)
Time frame: Up to 7 years
Investigator-assessed Duration of Response (DOR)
Time frame: 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)
Time frame: Up to 7 years
Time to Confirmed Deterioration (TTCD) in Pain
Time frame: From baseline until end of follow-up (up to 7 years)
TTCD in Physical Function
Time frame: From baseline until end of follow-up (up to 7 years)
TTCD in Role Function
Time frame: From baseline until end of follow-up (up to 7 years)
TTCD in Global Health Status
Time frame: From baseline until end of follow-up (up to 7 years)
Percentage of Participants with Adverse Events
Time frame: 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)
Time frame: 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)
Time frame: Up to 7 years
Change from Baseline in Symptomatic Treatment Toxicities as Assessed Through use of the PRO-CTCAE
Time frame: Baseline up to 7 years
Change from Baseline in Treatment Side-effect Bother as Assessed Through use of the FACT-G GP5 Item
Time frame: Baseline up to 7 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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 locations (51)

The Dignity Health Cancer Institute

Phoenix, Arizona, 85004

Recruiting

Disney Family Cancer Center

Burbank, California, 91505

Recruiting

Scripps Health

La Jolla, California, 92040

Recruiting

Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720

Recruiting

Ellison Institute of Technology

Los Angeles, California, 90064

Recruiting

Palo Alto Medical Foundation Research Center

Palo Alto, California, 94301

Recruiting

Kaiser Permanente - San Marcos

San Marcos, California, 92069

Recruiting

Palo Alto Medical Foundation Research Center

San Mateo, California, 94401

Recruiting

Palo Alto Medical Foundation Research Center

Sunnyvale, California, 94086

Recruiting

Cancer Specialists of North Florida - Jacksonville

Jacksonville, Florida, 32207

Recruiting

Tallahassee Memorial HealthCare

Tallahassee, Florida, 32308

Recruiting

Moffitt Cancer Center-McKinley Campus

Tampa, Florida, 33612

Recruiting

Cleveland Clinic Florida

Weston, Florida, 33331

Recruiting

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, 30060

Recruiting

Cancer Care Specialists of Central Illinois

O'Fallon, Illinois, 62269

Recruiting

Springfield Clinic

Springfield, Illinois, 62702

Recruiting

Carle Cancer Center

Urbana, Illinois, 61801

Recruiting

Baptist Health Lexington

Lexington, Kentucky, 40503

Recruiting

Baptist Health Hamburg

Lexington, Kentucky, 40509

Recruiting

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, 40536

Recruiting

University of Louisville Hospital

Louisville, Kentucky, 40202

Recruiting

Baptist Health Louisville

Louisville, Kentucky, 40207

Recruiting

Velocity Clinical Research

Annapolis, Maryland, 21401

Recruiting

University of Maryland

Baltimore, Maryland, 21201

Recruiting

Henry Ford Health System

Detroit, Michigan, 48202

Recruiting

Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503

Recruiting

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455

Recruiting

HCA Midwest Health

Kansas City, Missouri, 64132

Recruiting

Nebraska Cancer Specialists

Grand Island, Nebraska, 68803

Recruiting

Nebraska Cancer Specialists

Omaha, Nebraska, 68130-2042

Recruiting

Astera Cancer Care East Brunswick

East Brunswick, New Jersey, 08816

Recruiting

Summit Medical Group

Florham Park, New Jersey, 07932

Recruiting

The Blavatnik Family ? Chelsea Medical Center at Mount Sinai

New York, New York, 10011

Recruiting

Mount Sinai West

New York, New York, 10019

Recruiting

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting

Fairview Hospital

Cleveland, Ohio, 44111

Recruiting

Cleveland Clinic Foundation

Cleveland, Ohio, 44915

Recruiting

Hillcrest Hospital

Mayfield Heights, Ohio, 44124

Recruiting

Providence Portland Medical Center

Portland, Oregon, 97213

Recruiting

Providence Oncology and Hematology Cancer Clinic - Westside;Investigation Drug Services Pharmacy

Portland, Oregon, 97225

Recruiting

UPMC Hillman Cancer Center - Magee-Women?s Hospital

Pittsburgh, Pennsylvania, 15213

Recruiting

Bon Secours - St. Francis Hospital

Greenville, South Carolina, 29607

Recruiting

West Cancer Center

Germantown, Tennessee, 38138

Recruiting

Vanderbilt University Medical Center

Nashville, Tennessee, 37204

Recruiting

Community Clinical Trials

Kingwood, Texas, 77339

Recruiting

Swedish Cancer Institute - Edmonds Campus

Edmonds, Washington, 98026

Recruiting

Providence Regional Cancer Partnership

Everett, Washington, 98201-1621

Recruiting

Swedish Cancer Institute - Issaquah

Seattle, Washington, 98104

Recruiting

Swedish Cancer Institute

Seattle, Washington, 98104

Recruiting

Northwest Medical Specialties

Tacoma, Washington, 98405

Recruiting