Clinical trial NCT04025879: A Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Removal and Adjuvant Treatment With Nivolumab or Placebo for Participants With Surgically Removable Early Stage Non-small Cell Lung Cancer
Official title: A Phase 3, Randomized, Double-blind Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Resection and Adjuvant Treatment With Nivolumab or Placebo for Participants With Resectable Stage II-IIIB Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2019-07-19
Enrollment: 461
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: The main purpose of the study is to examine if periadjuvant (neoadjuvant, then adjuvant) immunotherapy will prolong event free survival in participants with early stage non-small cell lung cancer.


Eligibility criteria: Inclusion Criteria:

* Participants with suspected or histologically confirmed Stage IIA (\> 4 cm) to IIIB (T3N2) non-small cell lung carcinoma (NSCLC) with disease that is considered resectable
* No brain metastasis
* Treatment-naive for NSCLC (no prior systemic anti-cancer treatment)
* Ability to provide surgical or biopsy tumor tissue for biomarkers
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

Exclusion Criteria:

* Participants with an active, known or suspected autoimmune disease
* Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV)
* Any previous anti-cancer treatment including cytotoxic, IO treatment, targeted agents, or radiotherapy for NSCLC
* Prior treatment with any 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

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Event-Free Survival (EFS) by BICR
timeFrame: From randomization to disease progression, worsening, recurrence, or death due to any cause (up to approximately 44 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization and the date of death due to any cause.
measure: Pathologic Complete Response (pCR) Rate
timeFrame: From randomization up to approximately 44 months
measure: Major Pathological Response (MPR) Rate
timeFrame: From randomization up to approximately 44 months
measure: The Number of Participants With Adverse Events (AEs)
timeFrame: From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months)
measure: The Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months)
measure: The Number of Participants With Select Adverse Events (AEs)
timeFrame: From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months)
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Local Institution - 0104
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0040
state: Georgia
city: Augusta
country: United States
facility: Local Institution - 0120
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0145
state: Illinois
city: Chicago
country: United States
facility: Local Institution - 0078
state: Illinois
city: Orland Park
country: United States
facility: Local Institution - 0121
state: Illinois
city: Bethesda
country: United States
facility: Rcca Md Llc
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0074
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0076
state: Massachusetts
city: Traverse City
country: United States
facility: Local Institution - 0086
state: Michigan
city: Lebanon
country: United States
facility: Local Institution - 0100
state: New Hampshire
city: Cincinnati
country: United States
facility: Local Institution - 0055
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0102
state: Ohio
city: Houston
country: United States
facility: Local Institution - 0054
state: Texas
city: Fredericksburg
country: United States
facility: Local Institution - 0103
state: Virginia
city: Ciudad Autonoma Beunos Aires
country: Argentina
facility: Local Institution - 0032
state: Buenos Aires
city: ABB
country: Argentina
facility: Local Institution - 0031
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0043
city: Caba
country: Argentina
facility: Local Institution - 0030
city: Sydney
country: Australia
facility: Local Institution - 0020
state: New South Wales
city: Heidelberg
country: Australia
facility: Local Institution - 0033
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0122
state: Victoria
city: North Ballarat
country: Australia
facility: Local Institution - 0023
state: Victoria
city: Edegem
country: Belgium
facility: Local Institution - 0002
city: Liege
country: Belgium
facility: Local Institution - 0005
city: Roeselare
country: Belgium
facility: Local Institution - 0001
city: Belo Horizonte
country: Brazil
facility: Local Institution - 0035
state: Minas Gerais
city: Ijui
country: Brazil
facility: Local Institution - 0029
state: RIO Grande DO SUL
city: São Paulo
country: Brazil
facility: Local Institution - 0034
state: SAO Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution - 0036
state: São Paulo
city: São Paulo
country: Brazil
facility: Local Institution - 0106
city: Oshawa
country: Canada
facility: Local Institution - 0062
state: Ontario
city: Beijing
country: China
facility: Local Institution - 0115
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0096
state: BEI
city: Fuzhou
country: China
facility: Local Institution - 0137
state: Fujian
city: Fuzhou
country: China
facility: Local Institution - 0136
state: Fujian
city: Hubei Sheng
country: China
facility: Local Institution - 0151
state: Hubei
city: Changsha
country: China
facility: Local Institution - 0092
state: Hunan
city: Changsha
country: China
facility: Local Institution - 0093
state: Hunan
city: Changsha
country: China
facility: Local Institution - 0091
state: Hunan
city: Shanghai
country: China
facility: Local Institution - 0098
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0165
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0113
state: Shanghai
city: Chengdu
country: China
facility: Local Institution - 0088
state: Sichuan
city: Hangzhou
country: China
facility: Local Institution - 0099
state: Zhejiang
city: Shanghai
country: China
facility: Local Institution - 0095
city: Praha 2
country: Czechia
facility: Local Institution - 0041
city: Praha 4
country: Czechia
facility: Local Institution - 0042
city: Besancon
country: France
facility: Local Institution - 0073
city: La Tronche
country: France
facility: Local Institution - 0037
city: Montpellier
country: France
facility: Local Institution - 0050
city: Paris Cedex 18
country: France
facility: Local Institution - 0038
city: Paris Cedex 20
country: France
facility: Local Institution - 0051
city: Rennes Cedex 9
country: France
facility: Local Institution - 0083
city: Rouen
country: France
facility: Local Institution - 0146
city: Köln
country: Germany
facility: Local Institution - 0110
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Local Institution - 0085
city: Frankfurt
country: Germany
facility: Local Institution - 0065
city: Georgsmarienhuette
country: Germany
facility: Local Institution - 0072
city: Hamm
country: Germany
facility: Local Institution - 0071
city: Heidelberg
country: Germany
facility: Local Institution - 0108
city: Immenstadt
country: Germany
facility: Local Institution - 0109
city: Loewenstein
country: Germany
facility: Local Institution - 0064
city: Ludwigsburg
country: Germany
facility: Local Institution - 0147
city: Luebeck
country: Germany
facility: Local Institution - 0063
city: Moers
country: Germany
facility: Local Institution - 0070
city: Muenchen
country: Germany
facility: Local Institution - 0066
city: Dublin
country: Ireland
facility: Local Institution - 0016
city: Forlì
country: Italy
facility: Local Institution - 0024
city: Milano
country: Italy
facility: Local Institution - 0026
city: Parma
country: Italy
facility: Azienda Ospedaliera Di Parma
city: Nagoya-shi
country: Japan
facility: Local Institution - 0135
state: Aichi
city: Kashiwa-shi
country: Japan
facility: Local Institution - 0124
state: Chiba
city: Kitakyushu-shi
country: Japan
facility: Local Institution - 0129
state: Fukuoka
city: Kobe-shi
country: Japan
facility: Local Institution - 0127
state: Hyogo
city: Kanazawa-shi
country: Japan
facility: Local Institution - 0144
state: Ishikawa
city: Yokohama
country: Japan
facility: Local Institution - 0125
state: Kanagawa
city: Sendai-shi
country: Japan
facility: Local Institution - 0131
state: Miyagi
city: Sakai-shi
country: Japan
facility: Local Institution - 0126
state: Osaka
city: Kitaadachigun
country: Japan
facility: Local Institution - 0130
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0142
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0133
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0143
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0134
state: Tokyo
city: Fukushima-shi
country: Japan
facility: Local Institution - 0132
city: Hiroshima
country: Japan
facility: Local Institution - 0128
city: Guadalajara
country: Mexico
facility: Local Institution - 0077
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 0027
state: Nuevo Leon
city: Chihuahua
country: Mexico
facility: Local Institution - 0028
city: Groningen
country: Netherlands
facility: Local Institution - 0004
city: Rotterdam
country: Netherlands
facility: Local Institution - 0003
city: Kraków
country: Poland
facility: Local Institution - 0049
state: Małopolskie
city: Hato Rey
country: Puerto Rico
facility: Local Institution - 0117
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0013
state: Cluj
city: Bucuresti
country: Romania
facility: Local Institution - 0011
city: Floresti
country: Romania
facility: Local Institution - 0012
city: Moscow
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution - 0046
city: Majadahonda - Madrid
country: Spain
facility: Local Institution - 0044
city: Valencia
country: Spain
facility: Local Institution - 0045
city: Kaohsiung City
country: Taiwan
facility: Local Institution - 0149
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0119
city: New Taipei City
country: Taiwan
facility: Local Institution - 0116
city: Taipei City
country: Taiwan
facility: Local Institution - 0112
city: Taunton
country: United Kingdom
facility: Local Institution - 0007
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Leal TA, Ramalingam SS. Neoadjuvant therapy gains FDA approval in non-small cell lung cancer. Cell Rep Med. 2022 Jul 19;3(7):100691. doi: 10.1016/j.xcrm.2022.100691.
citation: Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022 Apr 1;82(7):1396-1408. doi: 10.1158/0008-5472.CAN-21-1382.