Clinical trial NCT04109066: Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Participants With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer
Official title: A Randomized, Multicenter, Double-blind, Placebo-controlled Phase 3 Study of Nivolumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy in Patients With High-risk, Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Primary Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Nivolumab
Breast Cancer
Cancer
Estrogen Receptor-Positive (ER+)
Human Epidermal Growth Factor 2 Negative (HER2-)
Neoadjuvant
Adjuvant
Primary Breast Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2019-09-30
Enrollment: 521
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: A randomized multi-arm study evaluating the efficacy and safety of nivolumab versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in participants with high-risk, estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) early stage breast cancer.


Eligibility criteria: Inclusion Criteria:

* Localized invasive breast ductal carcinoma, confirmed by the local pathologist, that includes the following combined primary tumor and clinical node (cN) categories: T1c (tumor size = 2 cm)-T2 (tumor size \> 2 cm), cN1-N2 OR T3-T4, cN0-cN2. Note: Axillary lymph node status must be assessed by fine needle biopsy or core biopsy.
* Estrogen receptor-positive (ER+) breast cancer (BC) and with or without progesterone receptor (PgR) expression (determined on the most recently analyzed tissue sample, tested locally, and confirmed by the central laboratory), as defined in the relevant American Society of Clinical Oncology (ASCO)- College of American Pathologists (CAP) Guidelines.
* Human epidermal growth factor receptor 2 (HER2-) BC tested in the local laboratory, defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+, or 2+.
* Tumor Grade 3 of ductal histology, Or Tumor Grade 2 of ductal histology having an ER expression level percentage between 1-10%
* Must agree to provide primary breast tumor tissue at baseline and at surgery
* Must be deemed eligible for surgery
* Males and females must agree to follow specific methods of contraception, if applicable, while participating in the trial
* Must have an Eastern Cooperative Oncology Group (ECOG) scale performance status of 0 or 1

Exclusion Criteria:

* Breastfeeding, pregnant, or expecting to conceive or father children within the projected duration of the study, starting with the screening through 12 months for participants who receive cyclophosphamide, or 6 months for participants who do not receive cyclophosphamide, after the last dose of study treatment
* Prior treatment with chemotherapy, endocrine therapy (ET), targeted therapy, and/or radiation therapy for the currently diagnosed breast cancer prior to enrollment
* Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
* Significant cardiovascular disease such as left ventricular ejection fraction (LVEF) \< 50% at baseline as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan performed at screening, or Class III or IV myocardial disease as described by the New York Heart Association
* History of ipsilateral invasive BC, regardless of treatment, ipsilateral ductal carcinoma in situ treated with radiation, or contralateral invasive BC, at any time
* Definitive clinical or radiologic evidence of metastatic disease
* Multicentric BC (the presence of \> 1 tumor in different quadrants of the breast)
* Bilateral invasive BC

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Pathological Complete Response (pCR) Rate
timeFrame: Up to approximately 37 months
Secondary outcomes:
measure: Pathological Complete Response (pCR) Rate (PD-L1 >=1%)
timeFrame: Up to approximately 37 months
measure: Number of Participants With Residual Cancer Burden (RCB)
timeFrame: Up to approximately 37 months
measure: Number of Participants With Residual Cancer Burden (RCB) PD-L1 >=1%
timeFrame: Up to approximately 37 months
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose to 30 days post last dose of neoadjuvant or adjuvant study therapy (Up to approximately 19 months)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first dose to 30 days post last dose of neoadjuvant or adjuvant study therapy (Up to approximately 19 months)
measure: Number of Participants Who Died
timeFrame: Up to approximately 41 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Local Institution - 0136
state: Alabama
city: Greenbrae
country: United States
facility: Local Institution - 0052
state: California
city: Whittier
country: United States
facility: Local Institution - 0051
state: California
city: Stamford
country: United States
facility: Local Institution - 0182
state: Connecticut
city: Jacksonville
country: United States
facility: Local Institution - 0150
state: Florida
city: Miami
country: United States
facility: Local Institution - 0097
state: Florida
city: Pensacola
country: United States
facility: Local Institution - 0149
state: Florida
city: Tallahassee
country: United States
facility: Local Institution - 0120
state: Florida
city: Athens
country: United States
facility: Local Institution - 0054
state: Georgia
city: Atlanta
country: United States
facility: Local Institution - 0107
state: Georgia
city: Columbus
country: United States
facility: Local Institution - 0056
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0221
state: Illinois
city: Fort Wayne
country: United States
facility: Local Institution - 0227
state: Indiana
city: Topsham
country: United States
facility: Local Institution - 0222
state: Maine
city: Bethesda
country: United States
facility: Local Institution - 0146
state: Maryland
city: Kansas City
country: United States
facility: HCA Midwest Division
state: Missouri
city: Florham Park
country: United States
facility: Local Institution - 0109
state: New Jersey
city: Hackensack
country: United States
facility: Local Institution - 0050
state: New Jersey
city: New Brunswick
country: United States
facility: Local Institution - 0180
state: New Jersey
city: Albuquerque
country: United States
facility: Local Institution - 0181
state: New Mexico
city: Bronx
country: United States
facility: Local Institution - 0041
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0283
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: Local Institution - 0053
state: Ohio
city: Nashville
country: United States
facility: Local Institution - 0218
state: Tennessee
city: Fort Worth
country: United States
facility: Local Institution - 0121
state: Texas
city: Fairfax
country: United States
facility: Local Institution - 0224
state: Virginia
city: Fredericksburg
country: United States
facility: Local Institution - 0122
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Local Institution - 0274
state: Washington
city: Ciudad Autonoma Beunos Aires
country: Argentina
facility: Local Institution - 0012
state: Buenos Aires
city: La Plata
country: Argentina
facility: Local Institution - 0015
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0020
state: Ciudad Autónoma De Buenos Aires
city: Córdoba
country: Argentina
facility: Local Institution - 0294
state: Cordoba
city: Río Cuarto
country: Argentina
facility: Local Institution - 0303
state: Cordoba
city: Caba
country: Argentina
facility: Local Institution - 0011
state: Distrito Federal
city: Capital Federal
country: Argentina
facility: Local Institution - 0008
state: Distrito Federal
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Local Institution - 0013
state: Distrito Federal
city: Rosario Santa Fe
country: Argentina
facility: Local Institution - 0014
state: Santa FE
city: Cordoba
country: Argentina
facility: Local Institution - 0021
city: La Rioja
country: Argentina
facility: Local Institution
city: Viedma
country: Argentina
facility: Local Institution
city: North Sydney
country: Australia
facility: Local Institution - 0071
state: New South Wales
city: Port Macquarie
country: Australia
facility: Local Institution - 0069
state: New South Wales
city: Herston
country: Australia
facility: Local Institution - 0072
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Local Institution - 0067
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 0066
state: Victoria
city: Clayton
country: Australia
facility: Local Institution - 0142
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0070
state: Victoria
city: North Ballarat
country: Australia
facility: Local Institution - 0068
state: Victoria
city: Graz
country: Austria
facility: Local Institution - 0045
city: Innsbruck
country: Austria
facility: Local Institution - 0042
city: Salzburg
country: Austria
facility: Local Institution - 0048
city: Wien
country: Austria
facility: Local Institution - 0046
city: Wien
country: Austria
facility: Local Institution - 0047
city: Brussels
country: Belgium
facility: Local Institution - 0187
city: Charleroi
country: Belgium
facility: Local Institution - 0030
city: Edegem
country: Belgium
facility: Local Institution - 0037
city: Gent
country: Belgium
facility: Local Institution - 0032
city: Liege
country: Belgium
facility: Local Institution - 0031
city: Fortaleza
country: Brazil
facility: Local Institution - 0130
state: Ceara
city: Brasilia
country: Brazil
facility: Local Institution - 0225
state: Distrito Federal
city: Goiânia
country: Brazil
facility: Local Institution - 0287
state: Goias
city: Belo Horizonte
country: Brazil
facility: Local Institution - 0133
state: Minas Gerais
city: Ijui
country: Brazil
facility: Local Institution - 0132
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0288
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0131
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution - 0135
state: RIO Grande DO SUL
city: Santa Cruz do Sul
country: Brazil
facility: Local Institution - 0273
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Local Institution - 0134
state: SAO Paulo
city: São Paulo
country: Brazil
facility: Local Institution - 0272
state: SAO Paulo
city: Santo André
country: Brazil
facility: Local Institution - 0128
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0129
city: São Paulo
country: Brazil
facility: Local Institution - 0144
city: São Paulo
country: Brazil
facility: Local Institution - 0104
city: Montreal
country: Canada
facility: Local Institution - 0194
state: Quebec
city: Montréal
country: Canada
facility: Local Institution - 0095
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution - 0058
state: Quebec
city: La Serena
country: Chile
facility: Local Institution - 0197
state: Coquimbo
city: Santiago de Chile
country: Chile
facility: Local Institution - 0016
state: Metropolitana
city: Santiago Region Metropolitana
country: Chile
facility: Local Institution - 0019
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0318
state: Metropolitana
city: Vina del Mar
country: Chile
facility: Local Institution - 0018
state: Valparaiso
city: Antofagasta
country: Chile
facility: Local Institution - 0326
city: Bengbu
country: China
facility: Local Institution - 0235
state: Anhui
city: Hefei
country: China
facility: Local Institution - 0239
state: Anhui
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Chongqing
country: China
facility: Local Institution - 0319
state: Chongqing
city: Chongqing
country: China
facility: Local Institution - 0232
state: Chongqing
city: Guangzhou
country: China
facility: Local Institution - 0267
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution - 0241
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Zunyi
country: China
facility: Local Institution - 0312
state: Guizhou
city: Shjiazhuang
country: China
facility: Local Institution - 0240
state: Hebei
city: Wuhan
country: China
facility: Local Institution - 0250
state: Hebei
city: Harbin
country: China
facility: Local Institution - 0248
state: Heilongjiang
city: Zhengzhou
country: China
facility: Local Institution
state: Henan
city: Changchun
country: China
facility: Local Institution - 0255
state: Jilin
city: Changchun
country: China
facility: Local Institution - 0247
state: Jilin
city: Shenyang
country: China
facility: Local Institution - 0252
state: Liaoning
city: Xian
country: China
facility: Local Institution - 0263
state: Shan3xi
city: Jinan
country: China
facility: Local Institution - 0245
state: Shandong
city: Qingdao
country: China
facility: Local Institution - 0256
state: Shandong
city: YanTai
country: China
facility: Local Institution - 0214
state: Shandong
city: Shanghai
country: China
facility: Local Institution - 0127
state: Shanghai
city: Chengdu
country: China
facility: Local Institution - 0244
state: Sichuan
city: Tianjin
country: China
facility: Local Institution - 0254
state: Tianjin
city: Urumqi
country: China
facility: Local Institution - 0311
state: Xinjiang
city: Hangzhou
country: China
facility: Local Institution - 0238
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 0231
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 0237
state: Zhejiang
city: Beijing
country: China
facility: Local Institution - 0215
city: Barranquilla
country: Colombia
facility: Local Institution - 0261
state: Atlántico
city: Colombia
country: Colombia
facility: Local Institution - 0203
state: Bogota
city: Montería
country: Colombia
facility: Local Institution - 0113
state: Córdoba
city: Bogotá
country: Colombia
facility: Local Institution - 0094
state: Distrito Capital De Bogotá
city: Piedecuesta
country: Colombia
facility: Local Institution - 0098
state: Santander
city: Cali
country: Colombia
facility: Local Institution - 0093
city: Pereira
country: Colombia
facility: Local Institution - 0271
city: Rionegro
country: Colombia
facility: Local Institution - 0202
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0100
city: Novy Jicin
country: Czechia
facility: Local Institution - 0103
city: Olomouc
country: Czechia
facility: Local Institution - 0101
city: Praha 10
country: Czechia
facility: Local Institution - 0099
city: Aarhus N
country: Denmark
facility: Local Institution - 0167
state: Midtjylland
city: Herlev
country: Denmark
facility: Local Institution - 0165
city: Kobenhavn O
country: Denmark
facility: Local Institution - 0164
city: Naestved
country: Denmark
facility: Local Institution - 0166
city: Helsinki
country: Finland
facility: Local Institution - 0001
city: Tampere
country: Finland
facility: Local Institution - 0160
city: Le Mans
country: France
facility: Local Institution - 0216
state: Sarthe
city: Besancon
country: France
facility: Local Institution - 0004
city: Brest
country: France
facility: Local Institution - 0024
city: Clermont-Ferrand
country: France
facility: Local Institution - 0162
city: Lyon
country: France
facility: Local Institution - 0153
city: Montpellier
country: France
facility: Local Institution - 0152
city: Paris
country: France
facility: Local Institution - 0161
city: Plerin
country: France
facility: Local Institution - 0195
city: Saint Herblain
country: France
facility: Local Institution - 0002
city: Strasbourg
country: France
facility: Local Institution - 0258
city: Toulon Cedex
country: France
facility: Local Institution - 0228
city: Villejuif
country: France
facility: Local Institution - 0003
city: München
country: Germany
facility: Local Institution - 0084
state: Bayern
city: Saarbruecken
country: Germany
facility: Local Institution - 0079
state: Saarland
city: Berlin
country: Germany
facility: Local Institution - 0083
city: Dresden
country: Germany
facility: Local Institution - 0112
city: Essen
country: Germany
facility: Local Institution - 0081
city: Frankfurt
country: Germany
facility: Local Institution - 0158
city: Hamburg
country: Germany
facility: Local Institution - 0223
city: Heidelberg
country: Germany
facility: Local Institution - 0087
city: Homburg
country: Germany
facility: Local Institution - 0089
city: Köln
country: Germany
facility: Local Institution - 0080
city: Leipzig
country: Germany
facility: Local Institution - 0196
city: Moenchengladbach
country: Germany
facility: Local Institution - 0111
city: Rostock
country: Germany
facility: Local Institution - 0156
city: Velbert
country: Germany
facility: Local Institution - 0157
city: Würzburg
country: Germany
facility: Local Institution - 0105
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0115
city: Dublin 8
country: Ireland
facility: Local Institution - 0034
state: Dublin
city: Beaumont
country: Ireland
facility: Local Institution - 0035
city: Cork
country: Ireland
facility: Local Institution - 0036
city: Catanzaro
country: Italy
facility: Local Institution - 0191
city: Milano
country: Italy
facility: Local Institution - 0207
city: Napoli
country: Italy
facility: Azienda Ospedaliero Universitaria Federico II di Napoli
city: Napoli
country: Italy
facility: Local Institution - 0124
city: Padova
country: Italy
facility: Local Institution - 0155
city: Pavia
country: Italy
facility: Fondazione Irccs - Policlinico San Matteo
city: Roma
country: Italy
facility: Local Institution - 0190
city: Rozzano (MI)
country: Italy
facility: Local Institution - 0125
city: Seongnam
country: Korea, Republic of
facility: Local Institution - 0325
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0295
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0320
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0290
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0291
city: Tijuana
country: Mexico
facility: Local Institution - 0262
state: BAJA California
city: Mexico City
country: Mexico
facility: Local Institution - 0168
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Local Institution - 0154
state: Distrito Federal
city: Zapopan
country: Mexico
facility: Local Institution - 0330
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 0137
state: Nuevo LEON
city: Merida
country: Mexico
facility: Local Institution - 0212
state: Yucatán
city: Campeche
country: Mexico
facility: Local Institution - 0280
city: Chihuahua
country: Mexico
facility: Local Institution - 0091
city: Colima
country: Mexico
facility: Local Institution - 0145
city: Oaxaca
country: Mexico
facility: Local Institution - 0141
city: Amsterdam
country: Netherlands
facility: Local Institution - 0033
city: Breda
country: Netherlands
facility: Local Institution - 0177
city: Deventer
country: Netherlands
facility: Local Institution - 0199
city: Utrecht
country: Netherlands
facility: Local Institution - 0147
city: Bydgoszcz
country: Poland
facility: Local Institution - 0335
city: Koszalin
country: Poland
facility: Local Institution - 0061
city: Krakow
country: Poland
facility: Local Institution - 0059
city: Lodz
country: Poland
facility: Local Institution - 0063
city: Opole
country: Poland
facility: Local Institution - 0062
city: Warszawa
country: Poland
facility: Local Institution - 0060
city: Gliwice
country: Poland
facility: Local Institution - 0334
state: Śląskie
city: Lisboa
country: Portugal
facility: Local Institution - 0210
city: Lisboa
country: Portugal
facility: Local Institution - 0211
city: Porto
country: Portugal
facility: Local Institution - 0209
city: Ponce
country: Puerto Rico
facility: Local Institution - 0110
city: Bucharest
country: Romania
facility: Local Institution - 0029
city: Bucharest
country: Romania
facility: Local Institution - 0270
city: Bucuresti
country: Romania
facility: Local Institution - 0025
city: Craiova
country: Romania
facility: Local Institution - 0028
city: Floresti
country: Romania
facility: Local Institution - 0027
city: Suceava
country: Romania
facility: Local Institution - 0026
city: Krasnodar
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution - 0119
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moskva
country: Russian Federation
facility: Local Institution - 0285
city: Ryazan
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution - 0284
city: Sankt-Peterburg
country: Russian Federation
facility: Local Institution - 0306
city: Sochi
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution - 0078
city: Singapore
country: Singapore
facility: Local Institution - 0076
city: Singapore
country: Singapore
facility: Local Institution - 0077
city: Elche
country: Spain
facility: Local Institution - 0205
state: Alicante
city: Barcelona
country: Spain
facility: Local Institution - 0171
city: Barcelona
country: Spain
facility: Local Institution - 0172
city: Madrid
country: Spain
facility: Local Institution - 0173
city: Madrid
country: Spain
facility: Local Institution - 0176
city: Malaga
country: Spain
facility: Local Institution - 0169
city: Pamplona
country: Spain
facility: Local Institution - 0204
city: Santiago de Compostela
country: Spain
facility: Local Institution - 0174
city: Sevilla
country: Spain
facility: Local Institution - 0170
city: Valencia
country: Spain
facility: Local Institution - 0175
city: Basel
country: Switzerland
facility: Local Institution - 0184
city: Lausanne
country: Switzerland
facility: Local Institution - 0186
city: Thun
country: Switzerland
facility: Local Institution - 0185
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0301
city: Tainan City
country: Taiwan
facility: Local Institution - 0300
city: Tainan
country: Taiwan
facility: Local Institution - 0298
city: Taipei
country: Taiwan
facility: Local Institution - 0305
city: Taipei
country: Taiwan
facility: Local Institution - 0297
city: Adana
country: Turkey
facility: Local Institution - 0073
city: Ankara
country: Turkey
facility: Local Institution - 0257
city: Antalya
country: Turkey
facility: Local Institution - 0075
city: Istanbul
country: Turkey
facility: Local Institution - 0074
city: Withington
country: United Kingdom
facility: Local Institution - 0006
state: Manchester
city: London
country: United Kingdom
facility: Local Institution - 0005
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: