A Study to Investigate Atezolizumab and Chemotherapy Compared With Placebo and Chemotherapy in the Neoadjuvant Setting in Participants With Early Stage Triple Negative Breast Cancer

NCT ID: NCT03197935

Last Updated: 2023-10-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

333 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-24

Study Completion Date

2022-09-28

Brief Summary

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This is a global Phase III, double-blind, randomized, placebo-controlled study designed to evaluate the efficacy and safety of neoadjuvant treatment with atezolizumab (anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) and nab-paclitaxel followed by doxorubicin and cyclophosphamide (nab-pac-AC), or placebo and nab-pac-AC in participants eligible for surgery with initial clinically assessed triple-negative breast cancer (TNBC).

Detailed Description

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Conditions

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Triple-negative 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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Atezolizumab and Chemotherapy

Participants received atezolizumab (840 milligrams \[mg\]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter \[mg/m\^2\]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants continued to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy.

Group Type EXPERIMENTAL

Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody

Intervention Type DRUG

Atezolizumab was administered as per schedule described in respective arm.

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel was administered as per schedule described in the arms.

Doxorubicin

Intervention Type DRUG

Doxorubicin was administered as per schedule described in the arms.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide was administered as per schedule described in the arms.

Filgrastim

Intervention Type DRUG

Filgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

Pegfilgrastim

Intervention Type DRUG

Pegfilgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

Placebo and Chemotherapy

Participants received placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m\^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m\^2) and cyclophosphamide (600 mg/m\^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo matched to atezolizumab was administered as per schedule described in respective arm.

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel was administered as per schedule described in the arms.

Doxorubicin

Intervention Type DRUG

Doxorubicin was administered as per schedule described in the arms.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide was administered as per schedule described in the arms.

Filgrastim

Intervention Type DRUG

Filgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

Pegfilgrastim

Intervention Type DRUG

Pegfilgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

Interventions

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Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody

Atezolizumab was administered as per schedule described in respective arm.

Intervention Type DRUG

Placebo

Placebo matched to atezolizumab was administered as per schedule described in respective arm.

Intervention Type DRUG

Nab-paclitaxel

Nab-paclitaxel was administered as per schedule described in the arms.

Intervention Type DRUG

Doxorubicin

Doxorubicin was administered as per schedule described in the arms.

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide was administered as per schedule described in the arms.

Intervention Type DRUG

Filgrastim

Filgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

Intervention Type DRUG

Pegfilgrastim

Pegfilgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically documented TNBC (negative human epidermal growth factor receptor 2 \[HER2\], estrogen receptor \[ER\], and progesterone receptor \[PgR\] status)
* Confirmed tumor programmed death-ligand 1 (PD-L1) evaluation as documented through central testing of a representative tumor tissue specimen
* Primary breast tumor size of greater than (\>) 2 centimeters (cm) by at least one radiographic or clinical measurement
* Stage at presentation: cT2-cT4, cN0-cN3, cM0
* Participant agreement to undergo appropriate surgical management including axillary lymph node surgery and partial or total mastectomy after completion of neoadjuvant treatment
* Baseline left ventricular ejection fraction (LVEF) greater than or equal to (\>=) 53 percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans
* Adequate hematologic and end-organ function
* Representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in paraffin blocks (preferred) or at least 20 unstained slides, with an associated pathology report documenting ER, PgR, and HER2 negativity
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
* Women who are not postmenopausal or have undergone a sterilization procedure must have a negative serum pregnancy test result within 14 days prior to initiation of study drug

Exclusion Criteria

* Prior history of invasive breast cancer
* Stage 4 (metastatic) breast cancer
* Prior systemic therapy for treatment and prevention of breast cancer
* Previous therapy with anthracyclines or taxanes for any malignancy
* History of ductal carcinoma in situ (DCIS), except for participants treated exclusively with mastectomy \>5 years prior to diagnosis of current breast cancer
* History of pleomorphic lobular carcinoma in situ (LCIS), except for participants surgically managed \>5 years prior to diagnosis of current breast cancer
* Bilateral breast cancer
* Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
* Axillary lymph node dissection prior to initiation of neoadjuvant therapy
* History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death
* Cardiopulmonary dysfunction
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
* Known allergy or hypersensitivity to the components of the formulations of atezolizumab, nab-paclitaxel, cyclophosphamide, or doxorubicin, filgrastim or pegfilgrastim
* Active or history of autoimmune disease or immune deficiency diseases except history of autoimmune-related hypothyroidism, controlled Type 1 diabetes mellitus, and dermatologic manifestations of eczema, psoriasis, lichen simplex chronicus, or vitiligo (e.g., participants with psoriatic arthritis are excluded)
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Positive human immunodeficiency virus (HIV) test at screening
* Active hepatitis B and hepatitis C virus infection
* Active tuberculosis
* Severe infections within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment, except prophylactic antibiotics
* Major surgical procedure within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
* Prior allogeneic stem cell or solid organ transplantation
* Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
* Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint-blockade therapies, including anti-cluster of differentiation 40 (anti-CD40), anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
* Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medications during the study
* History of cerebrovascular accident within 12 months prior to randomization
* Pregnant or lactating, or intending to become pregnant during the study
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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Stanford University Medical Center

Palo Alto, California, United States

Site Status

Norwalk Hospital

Norwalk, Connecticut, United States

Site Status

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital

Carrollton, Georgia, United States

Site Status

Mercy Medical Center

Baltimore, Maryland, United States

Site Status

HCA Midwest Division

Kansas City, Missouri, United States

Site Status

The Valley Hospital; Valley Medical Group

Paramus, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, United States

Site Status

The Center for Cancer and Blood Disorders - Fort Worth

Fort Worth, Texas, United States

Site Status

Cancer Care Northwest

Spokane, Washington, United States

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit

Bull Creek, Western Australia, Australia

Site Status

Cliniques Universitaires St-Luc

Brussels, , Belgium

Site Status

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status

Clinique Ste-Elisabeth

Namur, , Belgium

Site Status

Sint Augustinus Wilrijk

Wilrijk, , Belgium

Site Status

Santa Casa de Misericordia de Salvador

Salvador, Estado de Bahia, Brazil

Site Status

Hospital Araujo Jorge; Departamento de Ginecologia E Mama

Goiânia, Goiás, Brazil

Site Status

CETUS Hospital Dia Oncologia

Uberaba, Minas Gerais, Brazil

Site Status

Iop Instituto de Oncologia Do Parana

Curitiba, Paraná, Brazil

Site Status

Clinicas Oncologicas Integradas - COI

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

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

São Paulo, São Paulo, Brazil

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Hopital Sacre-Coeur Research Centre

Montreal, Quebec, Canada

Site Status

Hopital du Saint Sacrement

Québec, Quebec, Canada

Site Status

Hochwaldkrankenhaus

Bad Nauheim, , Germany

Site Status

Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)

Berlin, , Germany

Site Status

Ambulantes Tumorzentrum Spandau; Dres. Benno Mohr und Uwe Peters

Berlin, , Germany

Site Status

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, , Germany

Site Status

Luisenkrankenhaus GmbH & Co. KG., Brustzentrum

Düsseldorf, , Germany

Site Status

Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum

Gelsenkirchen, , Germany

Site Status

Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem

Hamburg, , Germany

Site Status

Diakovere Henriettenstift, Frauenklinik

Hanover, , Germany

Site Status

Dres. Andreas Köhler und Roswitha Fuchs

Langen, , Germany

Site Status

St. Elisabeth-Krankenhaus, Senologie/Brustzentrum

Leipzig, , Germany

Site Status

Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt

München, , Germany

Site Status

Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe

Münster, , Germany

Site Status

Medizinisches Versorgungszentrum am Klinikum Oldenburg GmbH

Oldenburg, , Germany

Site Status

Irccs Ospedale San Raffaele

Milan, Lombardy, Italy

Site Status

Ospedale San Gerardo

Monza, Lombardy, Italy

Site Status

Azienda ULSS 8 Berica; Oncologia Medica - Ospedlae di Vicenza

Vicenza, Veneto, Italy

Site Status

Aichi Cancer Center Hospital

Aichi, , Japan

Site Status

National Hospital Organization Shikoku Cancer Center

Ehime, , Japan

Site Status

Fukushima Medical University Hospital

Fukushima, , Japan

Site Status

Hiroshima City Hiroshima Citizens Hospital; Breast Surgery

Hiroshima, , Japan

Site Status

Kanagawa Cancer Center

Kanagawa, , Japan

Site Status

Tokai University Hospital

Kanagawa, , Japan

Site Status

National Hospital Organization Osaka National Hospital; Breast Surgery

Osaka, , Japan

Site Status

St. Luke's Internat. Hospital, Breast Surgical Oncology

Tokyo, , Japan

Site Status

The Cancer Inst. Hosp. of JFCR; Breast Oncology Center

Tokyo, , Japan

Site Status

Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr

Warsaw, , Poland

Site Status

Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii; Oddz. Onkologii Klin. i Chemioterapii

Wroc?aw, , Poland

Site Status

National Cancer Center

Goyang-si, , 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

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

Site Status

VETERANS GENERAL HOSPITAL; Department of General Surgery

Taipei, , Taiwan

Site Status

Mackay Memorial Hospital; Dept of Surgery

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation Linkou Branch

Taoyuan, , Taiwan

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

Barts & London School of Med; Medical Oncology

London, , United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Australia Belgium Brazil Canada Germany Italy Japan Poland South Korea Spain Taiwan United Kingdom

References

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Mittendorf EA, Assaf ZJ, Harbeck N, Zhang H, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Qamra A, Dieterich M, Xu Y, Liste-Hermoso M, Shearer-Kang E, Molinero L, Chui SY, Barrios CH. Peri-operative atezolizumab in early-stage triple-negative breast cancer: final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial. Nat Med. 2025 Jul;31(7):2397-2404. doi: 10.1038/s41591-025-03725-4. Epub 2025 Jun 4.

Reference Type DERIVED
PMID: 40467898 (View on PubMed)

Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Oct 10;396(10257):1090-1100. doi: 10.1016/S0140-6736(20)31953-X. Epub 2020 Sep 20.

Reference Type DERIVED
PMID: 32966830 (View on PubMed)

Perez-Garcia J, Soberino J, Racca F, Gion M, Stradella A, Cortes J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25.

Reference Type DERIVED
PMID: 32450725 (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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2016-004734-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO39392

Identifier Type: -

Identifier Source: org_study_id

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