A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer (IMpassion132)

A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study Of The Efficacy And Safety Of Atezolizumab Plus Chemotherapy For Patients With Early Relapsing Recurrent (Inoperable Locally Advanced Or Metastatic) Triple-Negative Breast Cancer

This study will evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with inoperable recurrent triple-negative breast cancer (TNBC).

Study Overview

• Status: Active, not recruiting
• Conditions: Triple Negative Breast Neoplasms
• Intervention / Treatment: Drug: Atezolizumab; Drug: Gemcitabine; Drug: Capecitabine; Drug: Carboplatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 572
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: MO39193 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABD
    • Fundación CENIT para la Investigación en Neurociencias
  • Rosario, Argentina, S2000KZE
    • Instituto De Oncologia De Rosario
  • Rosario, Argentina, S2002KDS
    • Hospital Provincial del Centenario
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Center of the Republic of Srpska
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Clinical Center University of Sarajevo
• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60135-237
      • Oncocentro Serviços Medicos E Hospitalares Ltda
  • GO
    • Goiania, GO, Brazil, 74605-070
      • Hospital Araujo Jorge; Departamento de Ginecologia E Mama
  • PE
    • Recife, PE, Brazil, 50040-000
      • Hospital do Cancer de Pernambuco - HCP
  • RS
    • Passo Fundo, RS, Brazil, 99010-090
      • Hospital Sao Vicente de Paulo
    • Porto Alegre, RS, Brazil, 90040-373
      • Hospital Nossa Senhora da Conceicao
  • SC
    • Chapeco, SC, Brazil, 89812-211
      • Centro de Oncologia de Santa Catarina LTDA
  • SP
    • Sao Paulo, SP, Brazil, 01317-000
      • Hospital Perola Byington
    • Sao Paulo, SP, Brazil, 04014-002
      • Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
    • Sao Paulo, SP, Brazil, 01229-010
      • Instituto de Pesquisa Grupo NotreDame Intermedica
• Chile
  • Puerto Montt, Chile, 5480000
    • Patagonia Research
  • Recoleta, Chile, 8420383
    • Bradford Hill Centro de Investigaciones Clinicas
  • Santiago, Chile, 7500921
    • Fundacion Arturo Lopez Perez
  • Santiago, Chile, 8241479
    • Clinica Vespucio
  • Temuco, Chile, 4800827
    • James Lind Centro de Investigacion del Cancer
  • Vina Del Mar, Chile, 2520598
    • ONCOCENTRO APYS; Oncología
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing City, China, 100021
    • Cancer Hospital , Chinese Academy of Medical
  • Bengbu City, China, 233000
    • The First Affiliated Hospital of Bengbu Medical College
  • Changchun, China, 132013
    • Jilin cancer hospital
  • Changsha CITY, China, 410013
    • Hunan Cancer hospital
  • Chongqing, China, 400016
    • The First Affiliated Hospital, Chongqing Medical University
  • Fuzhou City, China, 350001
    • Fujian Medical University Union Hospital
  • Guangzhou, China, 510000
    • Sun Yat-sen Memorial Hospital
  • Hangzhou City, China, 310016
    • Sir Run Run Shaw Hospital Zhejiang University
  • Harbin, China, 150081
    • Harbin medical university cancer hospital
  • Jinan, China, 250117
    • Shandong Cancer Hospital
  • Jinzhou City, China, 121001
    • The First Affiliated Hospital of Jinzhou Medical University
  • Nanjing, China, 210008
    • Jiangsu Province Hospital
  • Qingdao, China, 266003
    • The Affiliated Hospital of Medical College Qingdao University
  • Shanghai City, China, 201315
    • Fudan University Shanghai Cancer Center; Medical Oncology
  • Shenyang, China, 110001
    • First Hospital of China Medical University
  • Shijiazhuang, China, 050035
    • Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)
  • Taiyuan City, China, 030013
    • Shanxi Province Cancer Hospital
  • Tianjin, China, 300060
    • Tianjin cancer hospital
  • Xi'an, China, 710032
    • The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)
  • Zhejiang, China, 310022
    • Zhejiang Cancer Hospital
• Cuba
  • La Habana, Cuba, 10300
    • Hospital Hermanos Ameijeiras
  • La Habana, Cuba, 10400
    • Instituto Nacional de Oncología y Radiología (INOR)
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Central Hospital; Dept of Oncology
  • Tampere, Finland, 33520
    • Tampere University Hospital; Dept of Oncology
• France
  • Dijon, France, 21034
    • Centre Georges-François Lecler; Ctr de Lutte Contre le Canc
  • Lyon, France, 69373
    • Centre Leon Berard; Oncologie Genetique
  • Marseille Cedex 09, France, 13273
    • Institut Paoli-Calmettes; Oncologie Medicale 1
  • Montpellier, France, 34298
    • Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
  • Rennes, France, 35042
    • Centre Eugene Marquis; Service d'oncologie
  • St Cloud, France, 92210
    • INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale.
  • Vandoeuvre-les-nancy, France, 54519
    • Centre Alexis Vautrin; Oncologie Medicale
  • Villejuif, France, 94800
    • IGR
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe
  • Essen, Germany, 45136
    • Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
  • Frankfurt, Germany, 65929
    • Varisano Klinikum Frankfurt Höchst GmbH
  • Halle, Germany, 06120
    • Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe
  • Heidelberg, Germany, 69120
    • Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
  • München, Germany, 80638
    • Gemeinschaftspraxis Prof. Dr.med. Christoph Salat und Dr.med. Oliver J. Stötzer
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly
  • Budapest, Hungary, 1032
    • Szent Margit Hospital
  • Budapest, Hungary, 1145
    • Budapesti Uzsoki Utcai Korhaz
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz;Sugarterapias Klinikai Onkologiai Intez
  • Pécs, Hungary, 7623
    • Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Azienda Ospedaliero Universitaria San Martino
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele s.r.l.
    • Monza, Lombardia, Italy, 20900
      • Ospedale San Gerardo
  • Piemonte
    • Candiolo, Piemonte, Italy, 10060
      • Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
  • Puglia
    • Brindisi, Puglia, Italy, 72100
      • Ospedale Antonio Perrino; Oncologia Medica
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda
• Kazakhstan
  • Almaty, Kazakhstan, 050022
    • Kazakh Scientific Research Institution Of Oncology and Radiology
• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cancerologia; Oncology
  • Mexico City, Mexico, 03100
    • CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO
  • Mexico CITY (federal District)
    • Cdmx, Mexico CITY (federal District), Mexico, 06760
      • Centro Medico Dalinde
• Montenegro
  • Podgorica, Montenegro, 81000
    • Clinical Center of Montenegro; Clinic for Oncology and Radiotherapy
• Morocco
  • FES, Morocco, 30000
    • Centre Hospitalier Universitaire Hassan II
  • Marrakech, Morocco, 40000
    • Centre Hospitalier Universitaire Mohamed VI; Oncologie-Hématologie
  • Marrakech, Morocco, 40000
    • Clinique specialise Menara; Oncology Medical
  • Rabat, Morocco, 6213
    • Institut National D'oncologie Sidi Med Benabdellah
• Panama
  • Panama, Panama, 0832-02723
    • The Panama Clinic
• Peru
  • Lima, Peru, Lima 34
    • Instituto Nacional de Enfermedades Neoplasicas
• Poland
  • Kielce, Poland, 25-734
    • ?wi?tokrzyskie Centrum Onkologii; Dzia? Chemioterapii
  • Warszawa, Poland, 02-781
    • Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
• Portugal
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Oncologia Medica
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto ? Hospital de Santo António; Oncologia
• Russian Federation
  • Moskovskaja Oblast
    • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow City Oncology Hospital #62
    • Moscow, Moskovskaja Oblast, Russian Federation, 111123
      • Moscow Clinical Scientific Center
    • Moscow, Moskovskaja Oblast, Russian Federation, 115478
      • FSBI "National Medical Research Center of Oncology N.N. Blokhin?
  • Sankt Petersburg
    • Saint-Petersburg, Sankt Petersburg, Russian Federation
      • FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
    • Saint-Petersburg, Sankt Petersburg, Russian Federation, 198255
      • City Clinical Oncology Dispensary, SPb SBIH CCOD
    • St. Petersburg, Sankt Petersburg, Russian Federation, 195271
      • Private Healthcare Institution Clinical Hospital RZhD Medicine
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Oncology and Radiology of Serbia
  • Belgrade, Serbia, 11080
    • University Hospital Medical Center Bezanijska kosa
  • Nis, Serbia, 18000
    • Clinical Centre Nis, Clinic for Oncology
  • Sremska Kamenica, Serbia, 21204
    • Oncology Institute of Vojvodina
• Singapore
  • Singapore, Singapore, 168583
    • National Cancer Centre; Medical Oncology
• South Africa
  • Johannesburg, South Africa, 2196
    • Medical Oncology Centre of Rosebank; Oncology
  • Johannesburg, South Africa, 2193
    • Wits Clinical Research; Charlotte Maxeke Johannesburg Academic Hospital
  • Pretoria, South Africa, 0081
    • Private Oncology Centre
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Oncology
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia; Servicio de Oncología
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48903
      • Hospital de Cruces; Servicio de Oncologia
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty; Department of Internal Medicine
  • Ankara, Turkey, 06200
    • Ankara Oncology Hospital; Medical Oncology Department
  • Bornova, ?zm?r, Turkey, 35100
    • Ege University Medical Faculty; Medical Oncology Department
  • Edirne, Turkey, 22030
    • Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
  • Istanbul, Turkey, 34214
    • Medipol University Medical Faculty; Oncology Department
  • Istanbul, Turkey, 34890
    • Marmara University Pendik Training and Research Hospital; Medikal Onkoloji
  • Konya, Turkey, 42080
    • Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre; Oncology Dept
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital; Edinburgh Cancer Center
  • Lancaster, United Kingdom, LA1 4RP
    • Royal Lancaster Infirmary, Morecambe Bay Hospitals Nhs Trust
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust, Guys Hospital
  • London, United Kingdom, EC1M6BQ
    • Barts
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital NHS Trust
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon Cancer Centre
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Royal Stoke University Hospital
• United States
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists - Fort Myers (Broadway)
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists & Research Institute
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17109
      • Magee-Woman's Hospital; UPMC Pinnacle Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Woman's Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology; Sarah Cannon Research Institute
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
• Documented disease progression occurring within 12 months from the last treatment with curative intent
• Prior treatment (of early breast cancer) with an anthracycline and taxane
• Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted
• Measurable or non-measurable disease, as defined by RECIST 1.1
• Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used.
• Eastern Cooperative Oncology Group performance status 0-1
• Life expectancy ≥ 12 weeks
• Adequate haematologic and end-organ function
• Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
• The HBV DNA test will be performed only for patients who have a negative HBsAg and a positive HBcAb test.
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.
• Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period.
• Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm

Inclusion criteria for patients enrolled after the recruitment of all-comers is complete:

-PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells (IC) of 1% or greater.

Exclusion Criteria:

• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomisation
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• Symptomatic or rapid visceral progression
• No prior treatment with an anthracycline and taxane
• History of leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed)
• Uncontrolled tumour-related pain
• Uncontrolled or symptomatic hypercalcemia
• Malignancies other than TNBC within 5 years prior to randomisation)
• Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina
• Presence of an abnormal ECG
• Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
• Current treatment with anti-viral therapy for HBV.
• Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
• Treatment with investigational therapy within 28 days prior to randomisation
• Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of atezolizumab, or within 6 months after the last dose of capecitabine, whichever is later.

Exclusion Criteria Related to Atezolizumab:

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
• History of autoimmune disease
• Prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active tuberculosis
• Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo
• Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial

Exclusion Criteria Related to Capecitabine:

• Inability to swallow pills
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
• Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine

Exclusion Criteria Related to Carboplatin/Gemcitabine:

-Hypersensitivity to platinum containing compounds or any component of carboplatin or gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab; Participants will receive Atezolizumab on day 1 of each 3-week treatment cycle	Drug: Atezolizumab; Atezolizumab will be administered, 1200 mg by IV infusion with : gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle; Drug: Gemcitabine; Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle; Drug: Capecitabine; Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle; Drug: Carboplatin; Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle
Placebo Comparator: Placebo; Participants will receive Placebo on day 1 of each 3-week treatment cycle	Drug: Gemcitabine; Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle; Drug: Capecitabine; Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle; Drug: Carboplatin; Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle; Drug: Placebo; Placebo will be administered, 1200 mg by IV infusion with : gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	OS will be tested hierarchically in the following fixed order: In the population with programmed deathligand 1 (PD-L1)-positive tumour status; In the modified intent-to-treat (mITT) population	Baseline to end of study (approximately 58 months)
Overall Survival (OS) in Modified Intent-To-Treat (mITT) Popluation	OS will be tested hierarchically in the following fixed order: In the population with programmed deathligand 1 (PD-L1)-positive tumour status; In the modified intent-to-treat (mITT) population	Baseline to end of study (approximately 58 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Alive 12 Months		Randomization to 12 months post randomization
Proportion of Participants Alive 18 Months		Randomization to 18 months post randomization
Progression-Free Survival (PFS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first. PFS will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
Progression-Free Survival (PFS) in mITT population	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first. PFS will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
Objective Response Rate (ORR) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Objective Response Rate (ORR) in Modified Intent-To-Treat (mITT) Popluation	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Duration of Objective Response (DoR)	DoR as determined by the investigator according to RECIST 1.1.	Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Clinical Benefit Rate (CBR)	CBR is defined as the proportion of participants with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1.	8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)
Confirmed Objective Response Rate (C-ORR)		Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Duration of Response for Confirmed Responders (C-DoR)		Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Time to Confirmed Deterioration (TTD) of GHS/QoL	TTD of GHS/QoL, defined by a minimally important decrease of ≥10 points at two consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of the EORTC QLQ-C30.	Baseline to end of study (approximately 58 months)
Percentage of Participants With Adverse Events		Baseline to end of study (approximately 58 months)
Maximum Serum Concentration (Cmax) of Atezolizumab		At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)
Minimum Serum Concentration (Cmin) of Atezolizumab		At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)
Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab		Baseline to end of study (approximately 58 months)
Relationship Between PD-L1 Protein Expression in Screening Tumour Tissue and Clinical Outcomes		Baseline to end of study (approximately 58 months)
Overall Survival (OS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	OS will be tested hierarchically in the following fixed order: In the population with programmed deathligand 1 (PD-L1)-positive tumour status; In the modified intent-to-treat (mITT) population	Baseline to end of study (approximately 58 months)
Overall Survival (OS) in mITT China Popluation	OS will be tested hierarchically in the following fixed order: In the population with programmed deathligand 1 (PD-L1)-positive tumour status; In the modified intent-to-treat (mITT) population	Baseline to end of study (approximately 58 months)
Proportion of Participants Alive 12 Months in China Population		Randomization to 12 months post randomization
Proportion of Participants Alive 18 Months in China Population		Randomization to 18 months post randomization
Progression Free Survival (PFS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first. PFS will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
Progression Free Survival (PFS) in mITT China Population	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first. PFS will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
Objective Response Rate (ORR) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
ORR in Modified Intent-To-Treat (mITT) China Popluation	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Duration of Objective Response (DoR) in China Population	DoR as determined by the investigator according to RECIST 1.1.	Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Clinical Benefit Rate (CBR) in China Population	CBR is defined as the proportion of participants with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1.	8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)
Confirmed Objective Response Rate (C-ORR) in China Population		Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Duration of Response for Confirmed Responders (C-DoR) in China Population		Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Time to Confirmed Deterioration (TTD) of GHS/QoL in China Population	TTD of GHS/QoL, defined by a minimally important decrease of ≥10 points at two consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of the EORTC QLQ-C30.	Baseline to end of study (approximately 58 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2018
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Carboplatin; Capecitabine; Atezolizumab; Gemcitabine
• Other Study ID Numbers: MO39193; 2016-005119-42 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No