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

Breast Cancer Clinical Trial

— CheckMate 7FL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04109066
• Other study ID #: CA209-7FL
• Status: Completed
• Phase: Phase 3
• Start date: November 20, 2019
• Est. completion date: December 27, 2023

Study information

• Verified date: February 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 521
• Est. completion date: December 27, 2023
• Est. primary completion date: January 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• nivolumab
Specified Dose on Specified days

Drug:
• paclitaxel (PTX)
Specified dose on Specified days

Other:
• nivolumab placebo
Specified dose on Specified days

Drug:
• anthracycline
Specified dose on Specified days
• cyclophosphamide
Specified dose on Specified days
• Endocrine Therapy
Variable endocrine therapy of investigators choice

Procedure:
• Surgery
Surgery for breast cancer

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  Denmark,  Finland,  France,  Germany,  Hong Kong,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological Complete Response (pCR) Rate	pCR rate is defined as the percentage of participants who achieved pCR. pCR is defined as no invasive residual disease in breast and lymph nodes performed by a local pathologist. Criteria for evaluation of pCR includes the following: pCR in breast, axillary lymph nodes and non-axillary sentinel node; no histologic evidence of invasive tumor cells; and pCR in the breast.	Up to approximately 37 months
Secondary	Pathological Complete Response (pCR) Rate (PD-L1 >=1%)	pCR rate is defined as the percentage of participants who achieved pCR. pCR is defined as no invasive residual disease in breast and lymph nodes performed by a local pathologist. Criteria for evaluation of pCR includes the following: pCR in breast, axillary lymph nodes and non-axillary sentinel node; no histologic evidence of invasive tumor cells; and pCR in the breast.	Up to approximately 37 months
Secondary	Number of Participants With Residual Cancer Burden (RCB)	RCB is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. RCB is categorized into the following 4 classes: RCB-0: no residual disease; RCB-1: minimal residual disease; RCB-II: moderate residual disease; RCB-III: and extensive residual disease.	Up to approximately 37 months
Secondary	Number of Participants With Residual Cancer Burden (RCB) PD-L1 >=1%	RCB is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. RCB is categorized into the following 4 classes: RCB-0: no residual disease; RCB-1: minimal residual disease; RCB-II: moderate residual disease; RCB-III: and extensive residual disease.	Up to approximately 37 months
Secondary	Number of Participants With Adverse Events (AEs)	Number of participants with any grade adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relation with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From first dose to 30 days post last dose of neoadjuvant or adjuvant study therapy (Up to approximately 25 months)
Secondary	Number of Participants With Serious Adverse Events (SAEs)	Number of participants with any grade serious adverse events (SAE). SAE is defined as any untoward medical occurrence that, at any dose: Results in death; is life threatening; requires inpatient hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From first dose to 30 days post last dose of neoadjuvant or adjuvant study therapy (Up to approximately 25 months)
Secondary	Number of Participants Who Died	Number of participants who died due to any cause.	Up to approximately 37 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting