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NCT07405801PHASE2Recruiting

A Phase II Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus Ribociclib Plus Fulvestrant in Participants With Advanced Breast Cancer

Hoffmann-La Roche

Start Date

4/7/2026

Completion Date

2/26/2030

Summary

A study to evaluate the efficacy and safety of triplet combination of inavolisib plus ribociclib and fulvestrant versus placebo plus ribociclib and fulvestrant in the first-line setting in participants with endocrine-therapy-resistant hormone receptor (HR)-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC).

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Women or men with histologically or cytologically confirmed carcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent * Documented estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, defined as \>=1% of tumor cells stained positive based on the most recent tumor biopsy and assessed locally (Allison et al. 2020) * Participants must not have received any prior systemic therapy for locally advanced unresectable or metastatic breast cancer (mBC) and must have progressed during adjuvant endocrine-based treatment or within 12 months after completing adjuvant endocrine-based therapy with an aromatase inhibitor or tamoxifen * Confirmed biomarker eligibility as documented through central laboratory testing of a tumor tissue sample documenting both the lack of a phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation and the presence of heterozygous loss of chromosome 8p (i.e., PIK3CAnmd and chr8p loss) * Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) Exclusion Criteria: * Metaplastic breast cancer * Radiotherapy within 2 weeks before randomization * Appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines (e.g., participants with visceral crisis) * Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes * Known and untreated, or active Central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Participants with a history of treated CNS metastases are eligible * Any history of leptomeningeal disease or carcinomatous meningitis

Interventions

DRUG

Inavolisib

DRUG

Ribociclib

DRUG

Fulvestrant

DRUG

Placebo

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Conditions

Breast Cancer

Locations

Avera Cancer Institute - Marshall

Marshall, Minnesota 56258

United States

Avera Cancer Institute - Aberdeen

Aberdeen, South Dakota 57401

United States

Avera Cancer Institute - Mitchell

Mitchell, South Dakota 57301

United States

Avera Cancer Institute - Pierre, SD

Pierre, South Dakota 57501

United States

Avera Cancer Institute

Sioux Falls, South Dakota 57105

United States

AMG Oncology and Hematology Avera Cancer Institute - Yankton

Yankton, South Dakota 57078

United States

Inst. Alexander Fleming

Buenos Aires, C1426ANZ

Argentina

Centro Oncologico Korben

Caba, C1426AGE

Argentina

Centro Médico Fleischer

Capital Federal, C1414

Argentina

Sanatorio de la Mujer

Rosario, S2000ORE

Argentina

Hospital Santa Rita de Cassia Vitoria

Vitória, Espírito Santo 29043-260

Brazil

Hospital Brasilia

Brasília, Federal District 71.635-610

Brazil

ICTR Curitiba

Curitiba, Paraná 80510-130

Brazil

Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda

São Paulo, São Paulo 01317-000

Brazil

CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital

Chicoutimi, Quebec G7H 5H6

Canada

McGill University

Montreal, Quebec H4A 3J1

Canada

Centre Oscar Lambret

Lille, 59020

France

Centre Leon Berard

Lyon, 69008

France

Institut Paoli Calmettes

Marseille, 13273

France

Institut Régional du Cancer de Montpellier

Montpellier, 34298

France

Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)

Toulouse, 31059

France

Uniklinik RWTH Aachen Klinik für Gynäkologie und Geburtsmedizin

Aachen, 52074

Germany

Universitätsklinik Tübingen

Tübingen, 72076

Germany

Istituto Nazionale Tumori Irccs Fondazione g. PASCALE

Naples, Campania 80131

Italy

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola

Meldola, Emilia-Romagna 47014

Italy

Università Campus Bio-Medico di Roma

Rome, Lazio 128

Italy

Asst Papa Giovanni XXIII

Bergamo, Lombardy 24127

Italy

Ospedale San Raffaele

Milan, Lombardy 20132

Italy

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy 20133

Italy

Instituto Nacional De Cancerologia

Distrito Federal, Mexico CITY (federal District) 14000

Mexico

Centro de Investigacion Clinica de Oaxaca

Oaxaca City, Oaxaca 68020

Mexico

Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, 44280

Mexico

Instytut "Centrum Zdrowia Matki Polki"

?ód?, 93-338

Poland

Bialostockie Centrum Onkologii

Bialystok, 15-027

Poland

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, 20-090

Poland

Dolno?l?skie Centrum Onkologii

Wroc?aw, 53-413

Poland

Soon Chun Hyang University Cheonan Hospital

Dongnam-gu, Cheonan-si, 31151

South Korea

Gachon University Gil Medical Center

Namdong-Gu, 21565

South Korea

Seoul National University Bundang Hospital

Seongnam-si, 13605

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona 08908

Spain

Hospital Clinic Barcelona

Barcelona, 08036

Spain

Hospital Universitario Clínico San Cecilio

Granada, 18016

Spain

Hospital Ramon y Cajal

Madrid, 28034

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Clinico Universitario de Valencia

Valencia, 46010

Spain

Leicester Royal Infirmary

Leicester, LE1 5WWi

United Kingdom

Royal Free Hospital

London, NW3 2QG

United Kingdom

Christie Hospital Nhs Trust

Manchester, M20 4GJ

United Kingdom