A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT04191499

Last Updated: 2026-01-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

325 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-29

Study Completion Date

2027-11-15

Brief Summary

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This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Inavolisib + Palbociclib + Fulvestrant

Participants will receive inavolisib, palbociclib, and fulvestrant.

Group Type EXPERIMENTAL

Inavolisib

Intervention Type DRUG

Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.

Palbociclib

Intervention Type DRUG

Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.

Fulvestrant

Intervention Type DRUG

Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.

Placebo + Palbociclib + Fulvestrant

Participants will receive placebo, palbociclib, and fulvestrant. Participants randomized to the placebo arm who are still deriving benefit from the study treatment will be given an optional opportunity to crossover to the inavolisib arm.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will receive oral placebo on Days 1-28 of each 28-day cycle.

Palbociclib

Intervention Type DRUG

Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.

Fulvestrant

Intervention Type DRUG

Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.

Interventions

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Inavolisib

Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.

Intervention Type DRUG

Placebo

Participants will receive oral placebo on Days 1-28 of each 28-day cycle.

Intervention Type DRUG

Palbociclib

Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.

Intervention Type DRUG

Fulvestrant

Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.

Intervention Type DRUG

Other Intervention Names

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GDC-0077

Eligibility Criteria

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Inclusion Criteria

* Confirmed diagnosis of HR+/HER2- breast cancer
* Metastatic or locally advanced disease not amenable to curative therapy
* Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
* Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal
* Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
* Consent to provide fresh or archival tumor tissue specimen
* Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Life expectancy of \> 6 months
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria

* Metaplastic breast cancer
* Any history of leptomeningeal disease or carcinomatous meningitis
* Any prior systemic therapy for metastatic breast cancer
* Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
* Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
* 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 CNS metastases. Patients with a history of treated CNS metastases may be eligible
* Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period
* Symptomatic active lung disease, or requiring daily supplemental oxygen
* History of inflammatory bowel disease or active bowel inflammation
* Anti-cancer therapy within 2 weeks before study entry
* Investigational drug(s) within 4 weeks before randomization
* Prior radiotherapy to \>= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation
* Chronic corticosteroid therapy or immunosuppressants
* Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 2 weeks after the final dose of study treatment
* Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Beverly Hills Cancer Center

Beverly Hills, California, United States

Site Status

Massachusetts General Hospital.

Boston, Massachusetts, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Sarah Cannon Research Institute / Tennessee Oncology

Chattanooga, Tennessee, United States

Site Status

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Texas Oncology - Central South

Austin, Texas, United States

Site Status

Texas Tech University Health Sciences Center

El Paso, Texas, United States

Site Status

Texas Oncology - Northeast Texas

Tyler, Texas, United States

Site Status

Northwest Medical Specialties

Tacoma, Washington, United States

Site Status

Centro de Investigaciones Médicas y Desarrollo LC S.R.L

Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

Site Status

Centro Oncologico Korben

Ciudad Autonoma Buenos Aires, , Argentina

Site Status

Hosp Provincial D. Centenarios

Rosario, , Argentina

Site Status

Macquarie University Hospital

Macquarie Park, New South Wales, Australia

Site Status

Southern Medical Day Care Centre

Wollongong, New South Wales, Australia

Site Status

Mater Adult Hospital

South Brisbane, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Western Health

Fitzroy, Victoria, Australia

Site Status

Peninsula and South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Site Status

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Arthur J.E. Child Comprehensive Cancer Center-Calgary

Calgary, Alberta, Canada

Site Status

London Regional Cancer Program, London Health Sciences Centre, Baines Centre

London, Ontario, Canada

Site Status

Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status

Hopital du Saint Sacrement

Québec, Quebec, Canada

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

The First Hospital of Jilin University

Changchun, , China

Site Status

The First Affiliated Hospital, Chongqing Medical University

Chongqing, , China

Site Status

Fujian Medical University Union Hospital

Fujian, , China

Site Status

Sun Yet-sen University Cancer Center

Guangzhou, , China

Site Status

Zhejiang Cancer Hospital

Hangzhou, , China

Site Status

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status

Hebei Medical University Fourth Hospital

Shijiazhuang, , China

Site Status

Tianjin Cancer Hospital

Tianjin, , China

Site Status

Hubei Cancer Hospital

Wuhan, , China

Site Status

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, , China

Site Status

Henan Cancer Hospital

Zhengzhou, , China

Site Status

Vejle Sygehus

Vejle, , Denmark

Site Status

Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne

Clermont-Ferrand, , France

Site Status

Centre Georges Francois Leclerc

Dijon, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Hopital Prive Jean Mermoz

Lyon, , France

Site Status

Institut régional du Cancer Montpellier

Montpellier, , France

Site Status

Institut Universitaire du Cancer de Toulouse-Oncopole

Toulouse, , France

Site Status

Israel-Georgian Medical Research Clinic Healthycore

Tbilisi, , Georgia

Site Status

Tbilisi Oncology Dispensary

Tbilisi, , Georgia

Site Status

Ambulantes Tumorzentrum Spandau

Berlin, , Germany

Site Status

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH

Essen, , Germany

Site Status

Nationales Centrum für Tumorerkrankungen (NCT)

Heidelberg, , Germany

Site Status

Universitätsklinikum Mannheim

Mannheim, , Germany

Site Status

Klinikum Mutterhaus der Borromaeerinnen gGmbH

Trier, , Germany

Site Status

Universitätsfrauenklinik Ulm

Ulm, , Germany

Site Status

Anticancer Hospital Ag. Savas

Athens, , Greece

Site Status

Univ General Hosp Heraklion

Heraklion, , Greece

Site Status

Euromedical General Clinic of Thessaloniki

Thessaloniki, , Greece

Site Status

European Interbalkan Medical Center

Thessaloniki, , Greece

Site Status

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Orszagos Onkologiai Intezet

Budapest, , Hungary

Site Status

Uzsoki Utcai Korhaz

Budapest, , Hungary

Site Status

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, , Hungary

Site Status

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, Italy

Site Status

Az. Osp. Spedali Civili

Brescia, Lombardy, Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, Italy

Site Status

Ospedale Santa Maria Annunziata

Bagno a Ripoli, Tuscany, Italy

Site Status

IOV - Istituto Oncologico Veneto - IRCCS

Padua, Veneto, Italy

Site Status

National Cancer Institute IKN

Putrajaya, Federal Territory of Putrajaya, Malaysia

Site Status

Hospital Sultan Ismail

Johor Bahru, Johor, Malaysia

Site Status

Sarawak General Hospital

Sarawak, Sarawak, Malaysia

Site Status

Palmerston North Hospital

Palmerston North, , New Zealand

Site Status

Narodowy Instytut Onkologii Odzia? w Gliwicach

Gliwice, , Poland

Site Status

Przychodnia Lekarska KOMED, Roman Karaszewski

Konin, , Poland

Site Status

Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad

Warsaw, , Poland

Site Status

Centro Clinico Champalimaud

Lisbon, , Portugal

Site Status

IPO do Porto

Porto, , Portugal

Site Status

Moscow Clinical Scientific Center

Moscow, Moscow Oblast, Russia

Site Status

Blokhin Cancer Research Center

Moscow, Moscow Oblast, Russia

Site Status

LLC Medscan

Moskva, Moscow Oblast, Russia

Site Status

Clinical Hospital Lapino (LLC Haven)

Yudino, Moscow Oblast, Russia

Site Status

Medical Clinic "AB Medical group"

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

Volgograd Regional Clinical Oncology Dispensary

Volgograd, , Russia

Site Status

Regional Clinical Oncology Hospital

Yaroslavl, , Russia

Site Status

National University Hospital

Singapore, , Singapore

Site Status

National Cancer Centre

Singapore, , Singapore

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

Kyungpook National University Medical Center

Daegu, , South Korea

Site Status

National Cancer Center

Gyeonggi-do, , South Korea

Site Status

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Gangnam Severance Hospital

Seoul, , South Korea

Site Status

Ewha Womans University Mokdong Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

Site Status

Insituto Catalán de Oncologia (ICO)

Barcelona, , Spain

Site Status

Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico

Jaén, , Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Clinica Universidad de Navarra-Madrid

Madrid, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Puerta de Hierro

Madrid, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Instituto Valenciano Oncologia

Valencia, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Kaohsiung Medical Uni Chung-Ho Hospital

Kaohsiung City, , Taiwan

Site Status

Veterans General Hospital

Taipei, , Taiwan

Site Status

National Taiwan Uni Hospital

Taipei, , Taiwan

Site Status

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, , Taiwan

Site Status

Tri-Service General Hospital, Division of General Surgery

Taipei, , Taiwan

Site Status

Ramathibodi Hospital

Bangkok, , Thailand

Site Status

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Site Status

Chulabhorn Hospital

Lak Si, , Thailand

Site Status

Songklanagarind Hospital

Songkhla, , Thailand

Site Status

Adana Baskent University Hospital

Adana, , Turkey (Türkiye)

Site Status

Gulhane Training and Research Hospital

Ankara, , Turkey (Türkiye)

Site Status

Ege University Medical Faculty

Bornova, ?zm?r, , Turkey (Türkiye)

Site Status

Istanbul University Cerrahpasa Faculty of Medicine

Istanbul, , Turkey (Türkiye)

Site Status

Prof. Dr. Cemil Tascioglu City Hospital

Istanbul, , Turkey (Türkiye)

Site Status

SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU

Kharkiv, Kharkiv Governorate, Ukraine

Site Status

Municipal Institution SubCarpathian Clinical Oncological Centre

Ivano-Frankivsk, KIEV Governorate, Ukraine

Site Status

Uzhhorod Central City Clinical Hospital

Uzhhorod, KIEV Governorate, Ukraine

Site Status

City Clinical Hospital #4

Dnipropetrovsk, , Ukraine

Site Status

ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council

Kryvyi Rih, , Ukraine

Site Status

Kyiv City Clinical Oncological Center

Kyiv, , Ukraine

Site Status

Royal Marsden Hospital - Fulham

London, , United Kingdom

Site Status

Mount Vernon Hospital

Northwood, , United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Derriford Hospital

Plymouth, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Brazil Canada China Denmark France Georgia Germany Greece Hong Kong Hungary Italy Malaysia New Zealand Poland Portugal Russia Singapore South Korea Spain Taiwan Thailand Turkey (Türkiye) Ukraine United Kingdom

References

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Jhaveri KL, Im SA, Saura C, Loibl S, Kalinsky K, Schmid P, Loi S, Thanopoulou E, Shankar N, Jin Y, Stout TJ, Clark TD, Song C, Juric D, Turner NC. Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med. 2025 Jul 10;393(2):151-161. doi: 10.1056/NEJMoa2501796. Epub 2025 May 31.

Reference Type DERIVED
PMID: 40454641 (View on PubMed)

Turner NC, Im SA, Saura C, Juric D, Loibl S, Kalinsky K, Schmid P, Loi S, Sunpaweravong P, Musolino A, Li H, Zhang Q, Nowecki Z, Leung R, Thanopoulou E, Shankar N, Lei G, Stout TJ, Hutchinson KE, Schutzman JL, Song C, Jhaveri KL. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med. 2024 Oct 31;391(17):1584-1596. doi: 10.1056/NEJMoa2404625.

Reference Type DERIVED
PMID: 39476340 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2019-002455-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-505812-39-00

Identifier Type: CTIS

Identifier Source: secondary_id

WO41554

Identifier Type: -

Identifier Source: org_study_id

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