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)
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT04740918
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 96
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Trastuzumab Emtansine and Placebo 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. Arm A: Trastuzumab Emtansine and Placebo Trastuzumab Emtansine 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. Arm B: Trastuzumab Emtansine and Atezolizumab Trastuzumab Emtansine 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. Arm B: Trastuzumab Emtansine and Atezolizumab 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.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) as Determined by Investigator's Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Baseline until disease progression, death or end of study (approximately 78 months) 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.
Overall Survival (OS) From baseline until death or end of study (approximately 78 months) 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.
- Secondary Outcome Measures
Name Time Method 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) 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) From Cycle 1 until 3 months after study completion Following the Sponsor's decision to prematurely terminate the study, this analysis will not be conducted.
Cmax of Atezolizumab 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) 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.
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Trastuzumab Emtansine Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months) 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.
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) PFS as Determined by a Blinded Independent Central Review Committee Using RECIST v1.1 Baseline until disease progression, death or end of study (approximately 78 months) Following the Sponsor's decision to prematurely terminate the study, this analysis will not be conducted.
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 ADAs to Atezolizumab 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) 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.
Mean Change-From-Baseline Scores in Function (Physical, Role) and GHS/QoL as Measured by the EORTC QLQ-C30 From Cycle 1 until 3 months after study completion Following the Sponsor's decision to prematurely terminate the study, this analysis will not be conducted.
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) Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months) 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.
Percentage of Participants with Clinically Meaningful Deterioration in GHS/QoL Physical, and Role Function as Measured by the EORTC QLQ-C30 From Cycle 1 until 3 months after study completion Following the Sponsor's decision to prematurely terminate the study, this analysis will not be conducted.
Trial Locations
- Locations (50)
Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
🇹🇷Bakirkoy / Istanbul, Turkey
Acibadem University School of Medicine Altunizade Hospital Oncology Service
🇹🇷Istanbul, Turkey
Kayseri Acibadem Hospital
🇹🇷Kayseri, Turkey
UCL Hospital NHS Trust
🇬🇧London, United Kingdom
Guys and St Thomas NHS Foundation Trust, Guys Hospital
🇬🇧London, United Kingdom
Hospital do Cancer de Pernambuco - HCP
🇧🇷Recife, Pernambuco, Brazil
Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Núcleo de Pesquisa São Camilo
🇧🇷Sao Paulo, São Paulo, Brazil
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
🇨🇳Guangzhou City, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, China
Clinical Hospital Center Sestre Milosrdnice
🇭🇷Zagreb, Croatia
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Istituto Nazionale Tumori Irccs Fondazione g. PASCALE
🇮🇹Napoli, Campania, Italy
Oslo Universitetssykehus HF
🇳🇴Oslo, Norway
Cebu Doctors' University Hospital
🇵🇭Cebu City, Philippines
St. Luke's Medical Center
🇵🇭Quezon City, Philippines
Opolskie Centrum Onkologii
🇵🇱Opole, Poland
Centro Hospitalar do Porto ? Hospital de Santo António
🇵🇹Porto, Portugal
IPO do Porto
🇵🇹Porto, Portugal
Hospital Universitario Quiron Madrid
🇪🇸Pozuelo de Alarcón, Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Adana Baskent University Medical Faculty
🇹🇷Adana, Turkey
Katip Celebi University Ataturk Training and Research Hospital
🇹🇷Izmir, Turkey
Hacettepe Uni Medical Faculty Hospital
🇹🇷Sihhiye/Ankara, Turkey
Nottingham University Hospitals City Campus
🇬🇧Nottingham, United Kingdom
Emad Ibrahim, Md, Inc
🇺🇸Redlands, California, United States
Peter MacCallum Cancer Center
🇦🇺Melbourne, Victoria, Australia
Hospital Sao Rafael - HSR
🇧🇷Salvador, Bahia, Brazil
Hospital de Base de Sao Jose do Rio Preto
🇧🇷Sao Jose do Rio Preto, São Paulo, Brazil
Royal Victoria Hospital
🇨🇦Barrie, Ontario, Canada
Centre Hospitalier de l?Université de Montréal (CHUM)
🇨🇦Montreal, Quebec, Canada
Peking University People's Hospital
🇨🇳Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun City, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
🇨🇳Nanjing City, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjing, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
Clinica Vida
🇨🇴Medellin, Colombia
Oncomedica S.A.
🇨🇴Monteria, Colombia
Clinical Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Institut Curie - Hopital Rene Huguenin
🇫🇷Saint-Cloud, France
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati
🇮🇹Avellino, Campania, Italy
Azienda Ospedaliera S. Orsola-Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Centrum Onkologii ? Instytut im. Marii Sk?odowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
🇵🇱Warszawa, Poland
SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
🇷🇺Ufa, Baskortostan, Russian Federation
Sakarya Universitesi Egitim ve Arastirma Hastanesi
🇹🇷Adapazari/Sakarya, Turkey