Clinical trial NCT04740918: 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)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-02-05
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS) as Determined by Investigator's Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
timeFrame: Baseline until disease progression, death or end of study (approximately 78 months)
measure: Overall Survival (OS)
timeFrame: From baseline until death or end of study (approximately 78 months)
Secondary outcomes:
measure: Percentage of Participants With Objective Response Rate (ORR) as Determined by Investigator's Assessment Using RECIST v1.1
timeFrame: Baseline until disease progression, death or end of study (approximately 78 months)
measure: Duration of Objective Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1
timeFrame: Baseline until disease progression, death or end of study (approximately 78 months)
measure: PFS as Determined by a Blinded Independent Central Review Committee Using RECIST v1.1
timeFrame: Baseline until disease progression, death or end of study (approximately 78 months)
measure: PFS in Participants with Baseline Brain Metastases as Determined by Investigator Assessment Using RECIST v1.1
timeFrame: Baseline until disease progression, death or end of study (approximately 78 months)
measure: OS in Participants with Baseline Brain Metastases
timeFrame: From baseline until death or end of study (approximately 78 months)
measure: Central Nervous System (CNS) PFS as Determined by Investigator Assessment Using RECIST v1.1 in Participants with or Without Baseline CNS Metastases
timeFrame: Baseline until disease progression, death or end of study (approximately 78 months)
measure: 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)
timeFrame: From Cycle 1 until 3 months after study completion
measure: Mean Change-From-Baseline Scores in Function (Physical, Role) and GHS/QoL as Measured by the EORTC QLQ-C30
timeFrame: From Cycle 1 until 3 months after study completion
measure: Percentage of Participants with Clinically Meaningful Deterioration in GHS/QoL Physical, and Role Function as Measured by the EORTC QLQ-C30
timeFrame: From Cycle 1 until 3 months after study completion
measure: Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0
timeFrame: Baseline up to end of study (approximately 78 months)
measure: Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine
timeFrame: Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)
measure: Cmax of Atezolizumab
timeFrame: 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)
measure: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Trastuzumab Emtansine
timeFrame: Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)
measure: Percentage of Participants With ADAs to Atezolizumab
timeFrame: 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)
Other outcomes:
Locations:
city: Redlands
country: United States
facility: Emad Ibrahim, Md, Inc
state: California
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Recife
country: Brazil
facility: Hospital do Cancer de Pernambuco - HCP
state: Pernambuco
city: Ijui
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
state: Rio Grande Do Sul
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Núcleo de Pesquisa São Camilo
state: São Paulo
city: Barrie
country: Canada
facility: Royal Victoria Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l?Université de Montréal (CHUM)
state: Quebec
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Guangzhou City
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing City
country: China
facility: Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
city: Tianjing
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Medellin
country: Colombia
facility: Clinica Vida
city: Monteria
country: Colombia
facility: Oncomedica S.A.
city: Zagreb
country: Croatia
facility: Clinical Hospital Center Sestre Milosrdnice
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Saint-Cloud
country: France
facility: Institut Curie - Hopital Rene Huguenin
city: Avellino
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati
state: Campania
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione g. PASCALE
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliera S. Orsola-Malpighi
state: Emilia-Romagna
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF
city: Cebu City
country: Philippines
facility: Cebu Doctors' University Hospital
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
city: Opole
country: Poland
facility: Opolskie Centrum Onkologii
city: Warszawa
country: Poland
facility: Centrum Onkologii ? Instytut im. Marii Sk?odowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto ? Hospital de Santo António
city: Porto
country: Portugal
facility: IPO do Porto
city: Ufa
country: Russian Federation
facility: SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
state: Baskortostan
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quiron Madrid
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Adana
country: Turkey
facility: Adana Baskent University Medical Faculty
city: Adapazari/Sakarya
country: Turkey
facility: Sakarya Universitesi Egitim ve Arastirma Hastanesi
city: Bakirkoy / Istanbul
country: Turkey
facility: Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
city: Istanbul
country: Turkey
facility: Acibadem University School of Medicine Altunizade Hospital Oncology Service
city: Izmir
country: Turkey
facility: Katip Celebi University Ataturk Training and Research Hospital
city: Kayseri
country: Turkey
facility: Kayseri Acibadem Hospital
city: Sihhiye/Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital
city: London
country: United Kingdom
facility: UCL Hospital NHS Trust
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals City Campus
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: