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 (IMpassion031)
Triple-negative Breast Cancer
About this trial
This is an interventional treatment trial for Triple-negative Breast Cancer
Eligibility Criteria
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
Sites / Locations
- Stanford University Medical Center
- Norwalk Hospital
- Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
- Mercy Medical Center
- HCA Midwest Division
- The Valley Hospital; Valley Medical Group
- Memorial Sloan Kettering Cancer Center
- Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street
- Tennessee Oncology
- Vanderbilt Breast Center at One Hundred Oaks
- The Center for Cancer and Blood Disorders - Fort Worth
- Cancer Care Northwest
- Monash Medical Centre
- Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
- Cliniques Universitaires St-Luc
- UZ Leuven Gasthuisberg
- Clinique Ste-Elisabeth
- Sint Augustinus Wilrijk
- Santa Casa de Misericordia de Salvador
- Hospital Araujo Jorge; Departamento de Ginecologia E Mama
- CETUS Hospital Dia Oncologia
- Iop Instituto de Oncologia Do Parana
- Clinicas Oncologicas Integradas - COI
- Hospital Sao Lucas - PUCRS
- Hospital Nossa Senhora da Conceicao
- Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
- Jewish General Hospital
- Hopital Sacre-Coeur Research Centre
- Hopital du Saint Sacrement
- Hochwaldkrankenhaus
- Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)
- Ambulantes Tumorzentrum Spandau; Dres. Benno Mohr und Uwe Peters
- Onkologische Schwerpunktpraxis Bielefeld
- Luisenkrankenhaus GmbH & Co. KG., Brustzentrum
- Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum
- Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem
- Diakovere Henriettenstift, Frauenklinik
- Dres. Andreas Köhler und Roswitha Fuchs
- St. Elisabeth-Krankenhaus, Senologie/Brustzentrum
- Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt
- Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe
- Medizinisches Versorgungszentrum am Klinikum Oldenburg GmbH
- Irccs Ospedale San Raffaele
- Ospedale San Gerardo
- Azienda ULSS 8 Berica; Oncologia Medica - Ospedlae di Vicenza
- Aichi Cancer Center Hospital
- National Hospital Organization Shikoku Cancer Center
- Fukushima Medical University Hospital
- Hiroshima City Hiroshima Citizens Hospital; Breast Surgery
- Kanagawa Cancer Center
- Tokai University Hospital
- National Hospital Organization Osaka National Hospital; Breast Surgery
- St. Luke's Internat. Hospital, Breast Surgical Oncology
- The Cancer Inst. Hosp. of JFCR; Breast Oncology Center
- National Cancer Center
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center
- Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
- Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii; Oddz. Onkologii Klin. i Chemioterapii
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
- Hospital Universitario Virgen del Rocio; Servicio de Oncologia
- VETERANS GENERAL HOSPITAL; Department of General Surgery
- Mackay Memorial Hospital; Dept of Surgery
- Chang Gung Medical Foundation Linkou Branch
- Leicester Royal Infirmary
- Barts & London School of Med; Medical Oncology
- Freeman Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Atezolizumab and Chemotherapy
Placebo 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.
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.