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

NCT ID: NCT04109066

Last Updated: 2025-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 521 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-18
• Study Completion Date: 2023-12-27

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm A: Nivolumab combined with neoadjuvant CT and adjuvant ET

Nivolumab with paclitaxel followed by nivolumab with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then nivolumab with adjuvant (post-surgery) endocrine therapy of investigator's choice

Group Type: EXPERIMENTAL

nivolumab

Intervention Type: BIOLOGICAL

Specified Dose on Specified days

paclitaxel (PTX)

Intervention Type: DRUG

Specified dose on Specified days

anthracycline

Intervention Type: DRUG

Specified dose on Specified days

cyclophosphamide

Intervention Type: DRUG

Specified dose on Specified days

Endocrine Therapy

Intervention Type: DRUG

Variable endocrine therapy of investigators choice

Surgery

Intervention Type: PROCEDURE

Surgery for breast cancer

Arm B: Placebo combined with neoadjuvant CT and then adjuvant ET

Nivolumab placebo with paclitaxel followed by nivolumab placebo with anthracycline + cyclophosphamide as neoadjuvant (pre-surgery) treatment, then adjuvant (post-surgery) endocrine therapy of investigator's choice

Group Type: PLACEBO_COMPARATOR

paclitaxel (PTX)

Intervention Type: DRUG

Specified dose on Specified days

nivolumab placebo

Intervention Type: OTHER

Specified dose on Specified days

anthracycline

Intervention Type: DRUG

Specified dose on Specified days

cyclophosphamide

Intervention Type: DRUG

Specified dose on Specified days

Endocrine Therapy

Intervention Type: DRUG

Variable endocrine therapy of investigators choice

Surgery

Intervention Type: PROCEDURE

Surgery for breast cancer

Interventions

nivolumab

Specified Dose on Specified days

Intervention Type: BIOLOGICAL

paclitaxel (PTX)

Specified dose on Specified days

Intervention Type: DRUG

nivolumab placebo

Specified dose on Specified days

Intervention Type: OTHER

anthracycline

Specified dose on Specified days

Intervention Type: DRUG

cyclophosphamide

Specified dose on Specified days

Intervention Type: DRUG

Endocrine Therapy

Variable endocrine therapy of investigators choice

Intervention Type: DRUG

Surgery

Surgery for breast cancer

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 0136

Mobile, Alabama, United States

Local Institution - 0052

Greenbrae, California, United States

Local Institution - 0051

Whittier, California, United States

Local Institution - 0182

Stamford, Connecticut, United States

Local Institution - 0150

Jacksonville, Florida, United States

Local Institution - 0097

Miami, Florida, United States

Local Institution - 0149

Pensacola, Florida, United States

Local Institution - 0120

Tallahassee, Florida, United States

Local Institution - 0054

Athens, Georgia, United States

Local Institution - 0107

Atlanta, Georgia, United States

Local Institution - 0056

Columbus, Georgia, United States

Local Institution - 0221

Chicago, Illinois, United States

Local Institution - 0227

Fort Wayne, Indiana, United States

Local Institution - 0222

Topsham, Maine, United States

Local Institution - 0146

Bethesda, Maryland, United States

HCA Midwest Division

Kansas City, Missouri, United States

Local Institution - 0109

Florham Park, New Jersey, United States

Local Institution - 0050

Hackensack, New Jersey, United States

Local Institution - 0180

New Brunswick, New Jersey, United States

Local Institution - 0181

Albuquerque, New Mexico, United States

Local Institution - 0041

The Bronx, New York, United States

Local Institution - 0283

Charlotte, North Carolina, United States

Duke Cancer Institute

Durham, North Carolina, United States

Local Institution - 0053

Cleveland, Ohio, United States

Local Institution - 0218

Nashville, Tennessee, United States

Local Institution - 0121

Fort Worth, Texas, United States

Local Institution - 0224

Fairfax, Virginia, United States

Local Institution - 0122

Fredericksburg, Virginia, United States

Virginia Cancer Institute

Richmond, Virginia, United States

Local Institution - 0274

Seattle, Washington, United States

Local Institution - 0012

Ciudad Autonoma Beunos Aires, Buenos Aires, Argentina

Local Institution - 0015

La Plata, Buenos Aires, Argentina

Local Institution - 0020

Buenos Aires, Buenos Aires F.D., Argentina

Local Institution - 0294

Córdoba, Córdoba Province, Argentina

Local Institution - 0303

Río Cuarto, Córdoba Province, Argentina

Local Institution - 0013

Buenos Aires, Distrito Federal, Argentina

Local Institution - 0011

Caba, Distrito Federal, Argentina

Local Institution - 0008

Capital Federal, Distrito Federal, Argentina

Local Institution - 0014

Rosario Santa Fe, Santa Fe Province, Argentina

Local Institution - 0021

Córdoba, , Argentina

Local Institution

La Rioja, , Argentina

Local Institution

Viedma, , Argentina

Local Institution - 0071

North Sydney, New South Wales, Australia

Local Institution - 0069

Port Macquarie, New South Wales, Australia

Local Institution - 0072

Herston, Queensland, Australia

Local Institution - 0067

Elizabeth Vale, South Australia, Australia

Local Institution - 0066

Clayton, Victoria, Australia

Local Institution - 0142

Clayton, Victoria, Australia

Local Institution - 0070

Melbourne, Victoria, Australia

Local Institution - 0068

North Ballarat, Victoria, Australia

Local Institution - 0045

Graz, , Austria

Local Institution - 0042

Innsbruck, , Austria

Local Institution - 0048

Salzburg, , Austria

Local Institution - 0046

Vienna, , Austria

Local Institution - 0047

Vienna, , Austria

Local Institution - 0187

Brussels, , Belgium

Local Institution - 0030

Charleroi, , Belgium

Local Institution - 0037

Edegem, , Belgium

Local Institution - 0032

Ghent, , Belgium

Local Institution - 0031

Liège, , Belgium

Local Institution - 0130

Fortaleza, Ceará, Brazil

Local Institution - 0225

Brasília, Federal District, Brazil

Local Institution - 0287

Goiânia, Goiás, Brazil

Local Institution - 0133

Belo Horizonte, Minas Gerais, Brazil

Local Institution - 0132

Ijuí, Rio Grande do Sul, Brazil

Local Institution - 0288

Porto Alegre, Rio Grande do Sul, Brazil

Local Institution - 0131

Porto Alegre, Rio Grande do Sul, Brazil

Local Institution - 0135

Porto Alegre, Rio Grande do Sul, Brazil

Local Institution - 0273

Santa Cruz do Sul, Rio Grande do Sul, Brazil

Local Institution - 0134

Barretos, São Paulo, Brazil

Local Institution - 0128

Santo André, São Paulo, Brazil

Local Institution - 0272

São Paulo, São Paulo, Brazil

Local Institution - 0129

Rio de Janeiro, , Brazil

Local Institution - 0144

São Paulo, , Brazil

Local Institution - 0104

São Paulo, , Brazil

Local Institution - 0095

Montreal, Quebec, Canada

Local Institution - 0194

Montreal, Quebec, Canada

Local Institution - 0058

Sherbrooke, Quebec, Canada

Local Institution - 0197

La Serena, Coquimbo Region, Chile

Local Institution - 0018

Viña del Mar, Región de Valparaíso, Chile

Local Institution - 0016

Santiago, Santiago Metropolitan, Chile

Local Institution - 0318

Santiago, Santiago Metropolitan, Chile

Local Institution - 0019

Santiago Region Metropolitana, Santiago Metropolitan, Chile

Local Institution - 0326

Antofagasta, , Chile

Local Institution - 0235

Bengbu, Anhui, China

Local Institution - 0239

Hefei, Anhui, China

Local Institution

Beijing, Beijing Municipality, China

Local Institution - 0319

Chongqing, Chongqing Municipality, China

Local Institution - 0232

Chongqing, Chongqing Municipality, China

Local Institution - 0267

Guangzhou, Guangdong, China

Local Institution - 0241

Guangzhou, Guangdong, China

Local Institution

Guangzhou, Guangdong, China

Local Institution - 0312

Zunyi, Guizhou, China

Local Institution - 0240

Shjiazhuang, Hebei, China

Local Institution - 0250

Wuhan, Hebei, China

Local Institution - 0248

Harbin, Heilongjiang, China

Local Institution

Zhengzhou, Henan, China

Local Institution - 0255

Changchun, Jilin, China

Local Institution - 0247

Changchun, Jilin, China

Local Institution - 0252

Shenyang, Liaoning, China

Local Institution - 0263

Xi'an, Shan3xi, China

Local Institution - 0245

Jinan, Shandong, China

Local Institution - 0256

Qingdao, Shandong, China

Local Institution - 0214

Yantai, Shandong, China

Local Institution - 0127

Shanghai, Shanghai Municipality, China

Local Institution - 0244

Chengdu, Sichuan, China

Local Institution - 0254

Tianjin, Tianjin Municipality, China

Local Institution - 0311

Ürümqi, Xinjiang, China

Local Institution - 0238

Hangzhou, Zhejiang, China

Local Institution - 0231

Hangzhou, Zhejiang, China

Local Institution - 0237

Hangzhou, Zhejiang, China

Local Institution - 0215

Beijing, , China

Local Institution - 0261

Barranquilla, Atlántico, Colombia

Local Institution - 0094

Bogotá, Bogota D.C., Colombia

Local Institution - 0203

Colombia, Bogota D.C., Colombia

Local Institution - 0113

Montería, Departamento de Córdoba, Colombia

Local Institution - 0098

Piedecuesta, Santander Department, Colombia

Local Institution - 0093

Cali, , Colombia

Local Institution - 0271

Pereira, , Colombia

Local Institution - 0202

Rionegro, , Colombia

Local Institution - 0100

Hradec Králové, , Czechia

Local Institution - 0103

Nový Jičín, , Czechia

Local Institution - 0101

Olomouc, , Czechia

Local Institution - 0099

Prague, , Czechia

Local Institution - 0167

Aarhus N, Central Jutland, Denmark

Local Institution - 0165

Herlev, , Denmark

Local Institution - 0164

København Ø, , Denmark

Local Institution - 0166

Næstved, , Denmark

Local Institution - 0001

Helsinki, , Finland

Local Institution - 0160

Tampere, , Finland

Local Institution - 0216

Le Mans, Sarthe, France

Local Institution - 0004

Besançon, , France

Local Institution - 0024

Brest, , France

Local Institution - 0162

Clermont-Ferrand, , France

Local Institution - 0153

Lyon, , France

Local Institution - 0152

Montpellier, , France

Local Institution - 0161

Paris, , France

Local Institution - 0195

Plérin, , France

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Saint-Herblain, , France

Local Institution - 0258

Strasbourg, , France

Local Institution - 0228

Toulon, , France

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Villejuif, , France

Local Institution - 0084

München, Bavaria, Germany

Local Institution - 0079

Saarbrücken, Saarland, Germany

Local Institution - 0083

Berlin, , Germany

Local Institution - 0080

Cologne, , Germany

Local Institution - 0112

Dresden, , Germany

Local Institution - 0081

Essen, , Germany

Local Institution - 0158

Frankfurt, , Germany

Local Institution - 0223

Hamburg, , Germany

Local Institution - 0087

Heidelberg, , Germany

Local Institution - 0089

Homburg, , Germany

Local Institution - 0196

Leipzig, , Germany

Local Institution - 0111

Mönchengladbach, , Germany

Local Institution - 0156

Rostock, , Germany

Local Institution - 0157

Velbert, , Germany

Local Institution - 0105

Würzburg, , Germany

Local Institution - 0115

Hong Kong, , Hong Kong

Local Institution - 0034

Dublin, Dublin, Ireland

Local Institution - 0035

Beaumont, , Ireland

Local Institution - 0036

Cork, , Ireland

Local Institution - 0191

Catanzaro, , Italy

Local Institution - 0207

Milan, , Italy

Azienda Ospedaliero Universitaria Federico II di Napoli

Napoli, , Italy

Local Institution - 0124

Napoli, , Italy

Local Institution - 0155

Padua, , Italy

Fondazione Irccs - Policlinico San Matteo

Pavia, , Italy

Local Institution - 0190

Roma, , Italy

Local Institution - 0125

Rozzano (MI), , Italy

Local Institution - 0262

Tijuana, Estado de Baja California, Mexico

Local Institution - 0330

Zapopan, Jalisco, Mexico

Local Institution - 0168

Mexico City, Mexico City, Mexico

Local Institution - 0154

Mexico City, Mexico City, Mexico

Local Institution - 0137

Monterrey, Nuevo León, Mexico

Local Institution - 0212

Mérida, Yucatán, Mexico

Local Institution - 0280

Campeche, , Mexico

Local Institution - 0091

Chihuahua City, , Mexico

Local Institution - 0145

Colima, , Mexico

Local Institution - 0141

Oaxaca City, , Mexico

Local Institution - 0033

Amsterdam, , Netherlands

Local Institution - 0177

Breda, , Netherlands

Local Institution - 0199

Deventer, , Netherlands

Local Institution - 0147

Utrecht, , Netherlands

Local Institution - 0334

Gliwice, Silesian Voivodeship, Poland

Local Institution - 0335

Bydgoszcz, , Poland

Local Institution - 0061

Koszalin, , Poland

Local Institution - 0059

Krakow, , Poland

Local Institution - 0063

Lodz, , Poland

Local Institution - 0062

Opole, , Poland

Local Institution - 0060

Warsaw, , Poland

Local Institution - 0210

Lisbon, , Portugal

Local Institution - 0211

Lisbon, , Portugal

Local Institution - 0209

Porto, , Portugal

Local Institution - 0110

Ponce, , Puerto Rico

Local Institution - 0029

Bucharest, , Romania

Local Institution - 0025

Bucharest, , Romania

Local Institution - 0270

Bucharest, , Romania

Local Institution - 0028

Craiova, , Romania

Local Institution - 0027

Floreşti, , Romania

Local Institution - 0026

Suceava, , Romania

Local Institution

Krasnodar, , Russia

Local Institution - 0119

Moscow, , Russia

Local Institution

Moscow, , Russia

Local Institution - 0285

Moskva, , Russia

Local Institution

Ryazan, , Russia

Local Institution - 0306

Saint Petersburg, , Russia

Local Institution - 0284

Saint Petersburg, , Russia

Local Institution

Sochi, , Russia

Local Institution - 0078

Singapore, , Singapore

Local Institution - 0076

Singapore, , Singapore

Local Institution - 0077

Singapore, , Singapore

Local Institution - 0325

Seongnam, , South Korea

Local Institution - 0295

Seoul, , South Korea

Local Institution - 0320

Seoul, , South Korea

Local Institution - 0290

Seoul, , South Korea

Local Institution - 0291

Seoul, , South Korea

Local Institution - 0205

Elche, Alicante, Spain

Local Institution - 0171

Barcelona, , Spain

Local Institution - 0172

Barcelona, , Spain

Local Institution - 0173

Madrid, , Spain

Local Institution - 0176

Madrid, , Spain

Local Institution - 0169

Málaga, , Spain

Local Institution - 0204

Pamplona, , Spain

Local Institution - 0174

Santiago de Compostela, , Spain

Local Institution - 0170

Seville, , Spain

Local Institution - 0175

Valencia, , Spain

Local Institution - 0184

Basel, , Switzerland

Local Institution - 0186

Lausanne, , Switzerland

Local Institution - 0185

Thun, , Switzerland

Local Institution - 0301

Kaohsiung City, , Taiwan

Local Institution - 0298

Tainan City, , Taiwan

Local Institution - 0300

Tainan City, , Taiwan

Local Institution - 0305

Taipei, , Taiwan

Local Institution - 0297

Taipei, , Taiwan

Local Institution - 0073

Adana, , Turkey (Türkiye)

Local Institution - 0257

Ankara, , Turkey (Türkiye)

Local Institution - 0075

Antalya, , Turkey (Türkiye)

Local Institution - 0074

Istanbul, , Turkey (Türkiye)

Local Institution - 0006

Withington, Manchester, United Kingdom

Local Institution - 0005

London, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Chile; China; Colombia; Czechia; Denmark; Finland; France; Germany; Hong Kong; Ireland; Italy; Mexico; Netherlands; Poland; Portugal; Puerto Rico; Romania; Russia; Singapore; South Korea; Spain; Switzerland; Taiwan; Turkey (Türkiye); United Kingdom

References

Loi S, Salgado R, Curigliano G, Romero Diaz RI, Delaloge S, Rojas Garcia CI, Kok M, Saura C, Harbeck N, Mittendorf EA, Yardley DA, Suarez Zaizar A, Caminos FR, Ungureanu A, Reinoso-Toledo JG, Guarneri V, Egle D, Ades F, Pacius M, Chhibber A, Chandra R, Nathani R, Spires T, Wu JQ, Pusztai L, McArthur H. Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial. Nat Med. 2025 Feb;31(2):433-441. doi: 10.1038/s41591-024-03414-8. Epub 2025 Jan 21.

Reference Type: DERIVED

PMID: 39838118 (View on PubMed)

Schlam I, Corti C, Sammons S, Mittendorf EA, Tolaney SM. Checkpoint inhibition for early-stage hormone receptor-positive breast cancer. Expert Opin Biol Ther. 2024 Jun;24(6):511-520. doi: 10.1080/14712598.2024.2370395. Epub 2024 Jun 24.

Reference Type: DERIVED

PMID: 38913933 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

http://www.BMSClinicalTrials.com

BMS Clinical Trial Patient Recruiting

Other Identifiers

CA209-7FL

Identifier Type: -

Identifier Source: org_study_id