A Study of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo as a Treatment for Participants With Human Epidermal Growth Factor 2 (HER2)-Positive and Programmed Death-ligand 1 (PD-L1)-Positive Locally Advanced (LABC) or Metastatic Breast Cancer (MBC) (KATE3)

A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo in Patients With HER2-Positive and PD-L1-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab- (+/- Pertuzumab) and Taxane-Based Therapy (KATE3)

This study will evaluate the efficacy, safety and patient-reported outcomes of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo in participants with HER2-positive and PD-L1-positive LABC or MBC.Participants must have progressed either during or after prior trastuzumab- (+/- pertuzumab) and taxane-based therapy for LABC/MBC; or during (or within 6 months after completing) trastuzumab- (+/-pertuzumab) and taxane-based therapy in the neoadjuvant and/or adjuvant setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab Emtansine; Other: Placebo; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: MO42319 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • New South Wales
    • Gateshead, New South Wales, Australia, 2290
      • Lake Macquarie Private Hospital
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital; Oncology
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • North Melbourne, Victoria, Australia, 3051
      • Peter MacCallum Cancer Center
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
• Brazil
  • BA
    • Salvador, BA, Brazil, 41253-190
      • Hospital Sao Rafael - HSR
  • 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
    • Ijui, RS, Brazil, 98700-000
      • Hospital de Caridade de Ijui; Oncologia
    • Porto Alegre, RS, Brazil, 90040-373
      • Hospital Nossa Senhora da Conceicao
  • SP
    • Sao Jose do Rio Preto, SP, Brazil, 15090-000
      • Hospital de Base de São José do Rio Preto
    • Sao Paulo, SP, Brazil, 01317-001
      • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
    • Sao Paulo, SP, Brazil, 04014-002
      • Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa; Oncology
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre; Oncology
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center
    • Montreal, Quebec, Canada, H2X 0C2
      • Centre Hospitalier de l?Université de Montréal (CHUM)
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital; Research Unit
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CHUS (Centre Hospitalier Universitaire de Sherbrooke)
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Changchun City, China, 130021
    • The First Hospital of Jilin University
  • Changsha CITY, China, 410013
    • Hunan Cancer Hospital
  • Guangzhou City, China, 510120
    • Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Breast Tumor Center
  • Hangzhou, China, 310014
    • Zhejiang Provincial People's Hospital; Oncology& Breast
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Kunming City, China, 650100
    • Yunnan Cancer Hospital; Breast Surgery
  • Nanjing City, China, 210029
    • Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
  • Shenzhen, China, 518036
    • Peking University Shenzhen Hospital
  • Tianjin, China, 3000060
    • Tianjin Medical University Cancer Institute & Hospital
  • Wuhan City, China, 430023
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Xian, China, 710068
    • Shanxi Provincial People's Hospital
  • Zhejiang, China, 310022
    • Zhejiang Cancer Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• Colombia
  • Medellin, Colombia
    • Clinica Vida
  • Monteria, Colombia, 230002
    • Oncomedica S.A.
  • Pereira, Colombia, 600004
    • Oncólogos de Occidente
• Croatia
  • Split, Croatia, 21000
    • Clinical Hospital Centre Split
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Clinical Hospital Center Sestre Milosrdnice; Clinic for tumors
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Central Hospital; Dept of Oncology
  • Oulu, Finland, 90029
    • Oulu University Hospital; Oncology
  • Tampere, Finland, 33520
    • Tampere University Hospital; Dept of Oncology
• France
  • Amiens, France, 80054
    • CHU Amiens - Hopital Sud
  • Bordeaux, France, 33300
    • Polyclinique Bordeaux Nord Aquitaine
  • Grenoble, France, 38043
    • Chu Grenoble - Hopital Albert Michallon; Departement de Cancero-Hematologie
  • Lille, France, 59020
    • Centre Oscar Lambret; Senologie
  • Nice, France, 06189
    • Centre Antoine Lacassagne, Centre de Lutte Contre le Cancer (CLCC) de Nice
  • Paris, France, 75020
    • Groupe Hospitalier Diaconesses Croix Saint-Simon - Site Reuilly)
  • Poitiers, France, 86021
    • Chu La Miletrie; Oncologie Medicale
  • Saint-Cloud, France, 92211
    • Institut Curie - Hôpital René Huguenin
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer de Toulouse-Oncopole
• Greece
  • Athens, Greece, 115 22
    • Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine
  • Athens, Greece, 115 28
    • Alexandras General Hospital of Athens; Oncology Department
  • Heraklion, Crete, Greece, 711 10
    • University General Hospital of Heraklion;Internal Medicine-Oncology Clinic
  • Thessaloniki, Greece, 546 45
    • Euromedical General Clinic of Thessaloniki; Oncology Department
• Italy
  • Campania
    • Avellino, Campania, Italy, 83100
      • Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliera S. Orsola-Malpighi
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • Azienda Unità Sanitaria Locale di Reggio Emilia/IRCCS
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
• Norway
  • Oslo, Norway, 0450
    • Oslo Universitetssykehus HF; Ullevål sykehus
• Philippines
  • Cebu City, Philippines, 6000
    • Cebu Doctors' University Hospital; Research Office
  • Quezon City, Philippines, 1102
    • St. Luke's Medical Center; Human Cancer Biobank Research Center
  • San Juan, Philippines, 1502
    • Cardinal Santos Medical Center; Lower Ground Floor Research Room, Cancer Center
• Poland
  • ?ód?, Poland, 90-338
    • Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna
  • Gdansk, Poland, 80-219
    • Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
  • Konin, Poland, 62-500
    • Przychodnia Lekarska KOMED, Roman Karaszewski
  • Kraków, Poland, 30-688
    • Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
  • Opole, Poland, 45-061
    • Opolskie Centrum Onkologii;Oddzial Onkologii Klinicznej
  • Poznan, Poland, 60-569
    • Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna
  • Warszawa, Poland, 02-781
    • Centrum Onkologii ? Instytut im. Marii Sk?odowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
  • Wieliszew, Poland, 05-135
    • Mazowiecki Szpital Onkologiczny
• Portugal
  • Lisboa, Portugal, 1099-023
    • IPO de Lisboa; Servico de Oncologia Medica
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Oncologia Medica
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto ? Hospital de Santo António; Oncologia
• Russian Federation
  • Samara, Russian Federation, 443031
    • Samara Regional Oncology Dispensary
  • Saratov, Russian Federation, 410053
    • State Healthcare Institution ?Regional Clinical Oncology Dispensary?
  • Baskortostan
    • Ufa, Baskortostan, Russian Federation, 450054
      • SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 115478
      • FSBSI ?N. N. Blokhin Russian Cancer Research Center?
  • Sankt Petersburg
    • ST Petersburg, Sankt Petersburg, Russian Federation, 197758
      • St. Petersburg Clinical Scientific Center of special services medical assis (oncology)
    • Saint-Petersburg, Sankt Petersburg, Russian Federation, 198255
      • City Clinical Oncology Dispensary, SPb SBIH CCOD
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Institute Of Oncology Ljubljana
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Oncology
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Oncologia
  • Malaga, Spain, 29011
    • Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Castellon
    • Castellon de La Plana, Castellon, Spain, 12002
      • Hospital Provincial de Castellon; Servicio de Oncologia
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quiron Madrid; Servicio de Oncologia
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Complexo Hospitalario de Vigo. Hospital Álvaro Cunqueiro; Servicio de Oncología
• Turkey
  • Adana, Turkey, 01220
    • Adana Baskent University Medical Faculty; Oncology
  • Adapazari/Sakarya, Turkey, 54100
    • Sakarya Universitesi Egitim ve Arastirma Hastanesi
  • Ankara, Turkey, 06520
    • Memorial Ankara Hastanesi
  • Bakirkoy / Istanbul, Turkey, 34147
    • Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
  • Istanbul, Turkey, 34742
    • Acibadem University School of Medicine Altunizade Hospital Oncology Service
  • Izmir, Turkey, 35360
    • Katip Celebi University Ataturk Training and Research Hospital; Oncology
  • Kayseri, Turkey, 38000
    • Kayseri Acibadem Hospital
  • Sihhiye/Ankara, Turkey, 06230
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary NHS Trust
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust, Guys Hospital
  • London, United Kingdom, NW1 2PG
    • UCL Hospital NHS Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Milton Keynes, United Kingdom, MK6 5LD
    • Milton Keynes University Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals City Campus; Nottingham Cancer Clinical Trials Team
• United States
  • California
    • Redlands, California, United States, 92373
      • Emad Ibrahim, Md, Inc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• HER2+ and PD-L1+ locally advanced (LABC) or metastatic breast cancer (MBC)
• Progression must have occurred during most recent treatment for LABC/MBC or during, or within 6 months after completing, neoadjuvant and/or adjuvant therapy
• Prior treatment with trastuzumab (+/- pertuzumab) and taxane in the neoadjuvant and/or adjuvant, locally advanced, or metastatic setting
• No more than two prior lines of therapy in the metastatic setting
• Measurable disease per RESIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy >= 6 months
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

• Prior treatment with trastuzumab emtansine in metastatic setting
• History of exposure to cumulative doses of anthracyclines
• Symptomatic or actively progressing central nervous system (CNS) metastases; asymptomatic CNS lesions ≤ 2cm without clinical requirement for local intervention or asymptomatic patients with treated CNS lesions are eligible
• Current Grade >= 3 peripheral neuropathy
• Cardiopulmonary dysfunction
• History of malignancy within 5 years prior to initiation of study treatment, with the exception of the cancer under investigation and malignancies with a negligible risk of metastasis or death
• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• Active hepatitis B, hepatitis C and/or tuberculosis
• Prior allogeneic stem cell or solid organ transplantation
• Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, during treatment, or within 5 months following the last dose of study treatment
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Trastuzumab Emtansine and Placebo; Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor.	Drug: Trastuzumab Emtansine; Trastuzumab emtansine 3.6 mg/kg IV infusion; Other Names: Kadcyla, T-DM1, RO5304020; Other: Placebo; Placebo matched to atezolizumab
Experimental: Arm B: Trastuzumab Emtansine and Atezolizumab; Atezolizumab 1200 mg IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor.	Drug: Trastuzumab Emtansine; Trastuzumab emtansine 3.6 mg/kg IV infusion; Other Names: Kadcyla, T-DM1, RO5304020; Drug: Atezolizumab; Atezolizumab 1200 mg IV infusion; Other Names: Tecentriq, RO5541267, MPDL3280A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) as Determined by Investigator's Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)	Following the Sponsor's decision to prematurely terminate the study, no formal testing will be performed and the outcome measure will only be reported in a descriptive way.	Baseline until disease progression, death or end of study (approximately 78 months)
Overall Survival (OS)	Following the Sponsor's decision to prematurely terminate the study, no formal testing will be performed and the outcome measure will only be reported in a descriptive way.	From baseline until death or end of study (approximately 78 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR) as Determined by Investigator's Assessment Using RECIST v1.1		Baseline until disease progression, death or end of study (approximately 78 months)
Duration of Objective Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1		Baseline until disease progression, death or end of study (approximately 78 months)
PFS in Participants with Baseline Brain Metastases as Determined by Investigator Assessment Using RECIST v1.1		Baseline until disease progression, death or end of study (approximately 78 months)
OS in Participants with Baseline Brain Metastases		From baseline until death or end of study (approximately 78 months)
Central Nervous System (CNS) PFS as Determined by Investigator Assessment Using RECIST v1.1 in Participants with or Without Baseline CNS Metastases		Baseline until disease progression, death or end of study (approximately 78 months)
Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0		Baseline up to end of study (approximately 78 months)
PFS as Determined by a Blinded Independent Central Review Committee Using RECIST v1.1	Following the Sponsor's decision to prematurely terminate the study, this analysis will not be conducted.	Baseline until disease progression, death or end of study (approximately 78 months)
Mean Absolute Scores in Function (Physical, Role) and Global Health Status (GHS)/Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30)	Following the Sponsor's decision to prematurely terminate the study, this analysis will not be conducted.	From Cycle 1 until 3 months after study completion
Mean Change-From-Baseline Scores in Function (Physical, Role) and GHS/QoL as Measured by the EORTC QLQ-C30	Following the Sponsor's decision to prematurely terminate the study, this analysis will not be conducted.	From Cycle 1 until 3 months after study completion
Percentage of Participants with Clinically Meaningful Deterioration in GHS/QoL Physical, and Role Function as Measured by the EORTC QLQ-C30	Following the Sponsor's decision to prematurely terminate the study, this analysis will not be conducted.	From Cycle 1 until 3 months after study completion
Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine	Following the Sponsor's decision to prematurely terminate the study, this outcome measure is no longer applicable. Accordingly, the corresponding analysis will not be performed.	Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)
Cmax of Atezolizumab	Following the Sponsor's decision to prematurely terminate the study, this outcome measure is no longer applicable. Accordingly, the corresponding analysis will not be performed.	Day 1 of Cycles 1, 2, 3, 4 and 8 and every 8 cycles thereafter (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Trastuzumab Emtansine	Following the Sponsor's decision to prematurely terminate the study, this outcome measure is no longer applicable. Accordingly, the corresponding analysis will not be performed.	Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)
Percentage of Participants With ADAs to Atezolizumab	Following the Sponsor's decision to prematurely terminate the study, this outcome measure is no longer applicable. Accordingly, the corresponding analysis will not be performed.	Day 1 of Cycles 1, 2, 3, 4 and 8 and every 8 cycles thereafter (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 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): June 7, 2021
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Immunoconjugates; Immunotoxins; Trastuzumab; Maytansine; Atezolizumab; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: MO42319; 2020-002818-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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