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)

Metastatic Breast Cancer Clinical Trial

— KATE3  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04740918
• Other study ID #: MO42319
• Secondary ID: 2020-002818-41
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 7, 2021
• Est. completion date: April 30, 2024

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 96
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Trastuzumab Emtansine
Trastuzumab emtansine 3.6 mg/kg IV infusion
• Atezolizumab
Atezolizumab 1200 mg IV infusion

Other:
• Placebo
Placebo matched to atezolizumab

Locations

Country	Name	City	State
Australia	Lake Macquarie Private Hospital	Gateshead	New South Wales
Australia	Peter MacCallum Cancer Center	North Melbourne	Victoria
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Royal North Shore Hospital; Oncology	St. Leonards	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Brazil	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO
Brazil	Hospital de Caridade de Ijui; Oncologia	Ijui	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Hospital do Cancer de Pernambuco - HCP	Recife	PE
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP
Brazil	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP
Brazil	Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA	Sao Paulo	SP
Canada	Royal Victoria Hospital	Barrie	Ontario
Canada	Centre Hospitalier de l?Université de Montréal (CHUM)	Montreal	Quebec
Canada	McGill University Health Center	Montreal	Quebec
Canada	Jewish General Hospital; Research Unit	Montréal	Quebec
Canada	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario
Canada	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario
Canada	CHUS (Centre Hospitalier Universitaire de Sherbrooke)	Sherbrooke	Quebec
Canada	Sunnybrook Research Institute	Toronto	Ontario
China	Beijing Cancer Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	The First Hospital of Jilin University	Changchun City
China	Hunan Cancer Hospital	Changsha CITY
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Breast Tumor Center	Guangzhou City
China	Zhejiang Provincial People's Hospital; Oncology& Breast	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Yunnan Cancer Hospital; Breast Surgery	Kunming City
China	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City
China	Peking University Shenzhen Hospital	Shenzhen
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	Shanxi Provincial People's Hospital	Xian
China	Zhejiang Cancer Hospital	Zhejiang
China	Henan Cancer Hospital	Zhengzhou
Colombia	Clinica Vida	Medellin
Colombia	Oncomedica S.A.	Monteria
Colombia	Oncólogos de Occidente	Pereira
Croatia	Clinical Hospital Centre Split	Split
Croatia	Clinical Hospital Center Sestre Milosrdnice; Clinic for tumors	Zagreb
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Finland	Helsinki University Central Hospital; Dept of Oncology	Helsinki
Finland	Oulu University Hospital; Oncology	Oulu
Finland	Tampere University Hospital; Dept of Oncology	Tampere
France	CHU Amiens - Hopital Sud	Amiens
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Chu Grenoble - Hopital Albert Michallon; Departement de Cancero-Hematologie	Grenoble
France	Centre Oscar Lambret; Senologie	Lille
France	Centre Antoine Lacassagne, Centre de Lutte Contre le Cancer (CLCC) de Nice	Nice
France	Groupe Hospitalier Diaconesses Croix Saint-Simon - Site Reuilly)	Paris
France	Chu La Miletrie; Oncologie Medicale	Poitiers
France	Institut Curie - Hopital Rene Huguenin	Saint-Cloud
France	Institut Universitaire du Cancer de Toulouse-Oncopole	Toulouse
Greece	Alexandras General Hospital of Athens; Oncology Department	Athens
Greece	Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine	Athens
Greece	University General Hospital of Heraklion;Internal Medicine-Oncology Clinic	Heraklion, Crete
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
Italy	Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati	Avellino	Campania
Italy	Azienda Ospedaliera S. Orsola-Malpighi	Bologna	Emilia-Romagna
Italy	Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica	Napoli	Campania
Italy	Azienda Unità Sanitaria Locale di Reggio Emilia/IRCCS	Reggio Emilia	Emilia-Romagna
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Norway	Oslo Universitetssykehus HF; Ullevål sykehus	Oslo
Philippines	Cebu Doctors' University Hospital; Research Office	Cebu City
Philippines	St. Luke's Medical Center; Human Cancer Biobank Research Center	Quezon City
Philippines	Cardinal Santos Medical Center; Lower Ground Floor Research Room, Cancer Center	San Juan
Poland	Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna	?ód?
Poland	Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii	Gdansk
Poland	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin
Poland	Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii	Kraków
Poland	Opolskie Centrum Onkologii;Oddzial Onkologii Klinicznej	Opole
Poland	Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna	Poznan
Poland	Centrum Onkologii ? Instytut im. Marii Sk?odowskiej-Curie Klinika Nowotworów Piersi i Chirurgii	Warszawa
Poland	Mazowiecki Szpital Onkologiczny	Wieliszew
Portugal	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa
Portugal	IPO de Lisboa; Servico de Oncologia Medica	Lisboa
Portugal	Centro Hospitalar do Porto ? Hospital de Santo António; Oncologia	Porto
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Russian Federation	FSBSI ?N. N. Blokhin Russian Cancer Research Center?	Moscow	Moskovskaja Oblast
Russian Federation	City Clinical Oncology Dispensary, SPb SBIH CCOD	Saint-Petersburg	Sankt Petersburg
Russian Federation	Samara Regional Oncology Dispensary	Samara
Russian Federation	State Healthcare Institution ?Regional Clinical Oncology Dispensary?	Saratov
Russian Federation	St. Petersburg Clinical Scientific Center of special services medical assis (oncology)	ST Petersburg	Sankt Petersburg
Russian Federation	SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan	Ufa	Baskortostan
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Spain	Hospital Universitario Quiron Madrid; Servicio de Oncologia	Pozuelo de Alarcón	Madrid
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Complexo Hospitalario de Vigo. Hospital Álvaro Cunqueiro; Servicio de Oncología	Vigo	Pontevedra
Turkey	Adana Baskent University Medical Faculty; Oncology	Adana
Turkey	Sakarya Universitesi Egitim ve Arastirma Hastanesi	Adapazari/Sakarya
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji	Bakirkoy / Istanbul
Turkey	Acibadem University School of Medicine Altunizade Hospital Oncology Service	Istanbul
Turkey	Katip Celebi University Ataturk Training and Research Hospital; Oncology	Izmir
Turkey	Kayseri Acibadem Hospital	Kayseri
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
United Kingdom	Leicester Royal Infirmary NHS Trust	Leicester
United Kingdom	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London
United Kingdom	UCL Hospital NHS Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Milton Keynes University Hospital	Milton Keynes
United Kingdom	Nottingham University Hospitals City Campus; Nottingham Cancer Clinical Trials Team	Nottingham
United States	Emad Ibrahim, Md, Inc	Redlands	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China,  Colombia,  Croatia,  Finland,  France,  Greece,  Italy,  Korea, Republic of,  Norway,  Philippines,  Poland,  Portugal,  Russian Federation,  Slovenia,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	OS in Participants with Baseline Brain Metastases		From baseline until death or end of study (approximately 78 months)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)