Clinical trial NCT04026412: A Study of Nivolumab and Ipilimumab in Untreated Participants With Stage 3 Non-small Cell Lung Cancer (NSCLC) That is Unable or Not Planned to be Removed by Surgery
Official title: A Phase 3, Randomized, Open Label Study to Compare Nivolumab Plus Concurrent Chemoradiotherapy (CCRT) Followed by Nivolumab Plus Ipilimumab or Nivolumab Plus CCRT Followed by Nivolumab vs CCRT Followed by Durvalumab in Previously Untreated, Locally Advanced Non-small Cell Lung Cancer (LA NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2019-07-19
Enrollment: 925
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 primary purpose of the study is to compare the effectiveness of nivolumab plus concurrent chemoradiotherapy (CCRT) followed by nivolumab plus ipilimumab vs CCRT followed by durvalumab in participants with untreated Locally Advanced Non-small Cell Lung Cancer (LA NSCLC).


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Locally advanced stage IIIA, IIIB, or IIIC (T1-2 N2-3 M0, T3 N1-3 M0, or T4 N0-3 M0) pathologically-confirmed NSCLC, according to 8th TNM classification. Participants who are not planned for potential curative surgical resection are eligible.
* Newly diagnosed and treatment-naïve, with no prior local or systemic anticancer therapy given as primary therapy for locally advanced disease

Exclusion Criteria:

* Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator would preclude the participant from adhering to the protocol or would increase the risk associated with study participation
* Active infection requiring systemic therapy within 14 days prior to randomization
* History of organ or tissue transplant that requires systemic use of immune suppressive agents
* Prior thoracic radiotherapy

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Progression-free survival (PFS) by RECIST 1.1 per Blinded Independent Central Review (BICR) for Arm A vs Arm C
timeFrame: Up to 7 years
Secondary outcomes:
measure: Overall Survival (OS) for Arm A vs Arm C
timeFrame: Up to 7 years
measure: PFS by RECIST 1.1 per BICR for Arm B vs Arm C
timeFrame: Up to 7 years
measure: OS for Arm B vs Arm C
timeFrame: Up to 7 years
measure: PFS by RECIST 1.1 per BICR for Arm A vs Arm B
timeFrame: Up to 7 years
measure: OS for Arm A vs Arm B
timeFrame: Up to 7 years
measure: Objective Response Rate (ORR) by RECIST 1.1 per BICR
timeFrame: Up to 7 years
measure: Duration of Response (DoR) by RECIST 1.1 per BICR
timeFrame: Up to 7 years
measure: Time to Response (TTR) by RECIST 1.1 per BICR
timeFrame: Up to 7 years
measure: PFS by RECIST 1.1 per Investigator assessment
timeFrame: Up to 7 years
measure: ORR by RECIST 1.1 per Investigator assessment
timeFrame: Up to 7 years
measure: DoR by RECIST 1.1 per Investigator assessment
timeFrame: Up to 7 years
measure: TTR by RECIST 1.1 per Investigator assessment
timeFrame: Up to 7 years
measure: Time to Death or Distant Metastases (TTDM) by RECIST 1.1 per Investigator assessment
timeFrame: Up to 7 years
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 7 years
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: Up to 7 years
measure: Incidence of select AEs
timeFrame: Up to 7 years
measure: Proportion of participants without symptom deterioration based on NSCLC-SAQ
timeFrame: Up to 7 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Local Institution - 0119
state: California
city: San Francisco
country: United States
facility: Local Institution - 0207
state: California
city: San Francisco
country: United States
facility: Local Institution - 0166
state: California
city: Lone Tree
country: United States
facility: Local Institution - 0129
state: Colorado
city: Jacksonville
country: United States
facility: Local Institution - 0233
state: Florida
city: Orlando
country: United States
facility: Local Institution - 0219
state: Florida
city: Pensacola
country: United States
facility: Local Institution - 0039
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0125
state: Georgia
city: Augusta
country: United States
facility: Local Institution - 0165
state: Georgia
city: Edgewood
country: United States
facility: Local Institution - 0218
state: Kentucky
city: Bethesda
country: United States
facility: Local Institution - 0108
state: Maryland
city: Traverse City
country: United States
facility: Local Institution - 0116
state: Michigan
city: Cincinnati
country: United States
facility: Local Institution - 0053
state: Ohio
city: Cincinnati
country: United States
facility: Local Institution - 0131
state: Ohio
city: Cincinnati
country: United States
facility: Local Institution - 0188
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0112
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0124
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0047
state: Ohio
city: Youngstown
country: United States
facility: Local Institution - 0123
state: Ohio
city: Charleston
country: United States
facility: Local Institution - 0077
state: South Carolina
city: Austin
country: United States
facility: Local Institution - 0191
state: Texas
city: Bryan
country: United States
facility: Local Institution - 0079
state: Texas
city: Dallas
country: United States
facility: Local Institution - 0130
state: Texas
city: Burlington
country: United States
facility: Local Institution - 0071
state: Vermont
city: Caba
country: Argentina
facility: Local Institution - 0044
state: Buenos Aires
city: Río Cuarto
country: Argentina
facility: Local Institution - 0045
state: Cordoba
city: Buenos Aires
country: Argentina
facility: Local Institution - 0043
state: Distrito Federal
city: Caba
country: Argentina
facility: Local Institution - 0042
state: Distrito Federal
city: Darlinghurst
country: Australia
facility: Local Institution - 0031
state: New South Wales
city: Gosford
country: Australia
facility: Local Institution - 0134
state: New South Wales
city: Kingswood
country: Australia
facility: Local Institution - 0033
state: New South Wales
city: Greenslopes
country: Australia
facility: Local Institution - 0029
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution - 0028
state: South Australia
city: Ballarat Central
country: Australia
facility: Local Institution - 0224
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0052
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Murdoch
country: Australia
facility: Local Institution - 0030
state: Western Australia
city: Bruxelles
country: Belgium
facility: Local Institution - 0003
city: Gent
country: Belgium
facility: Local Institution - 0001
city: Liege
country: Belgium
facility: Local Institution - 0004
city: Yvoir
country: Belgium
facility: Local Institution - 0002
city: Ipatinga
country: Brazil
facility: Local Institution - 0038
state: Minas Gerais
city: Ijui
country: Brazil
facility: Local Institution - 0234
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0034
state: RIO Grande DO SUL
city: Blumenau
country: Brazil
facility: Local Institution - 0037
state: Santa Catarina
city: Barretos
country: Brazil
facility: Local Institution - 0036
state: SAO Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0035
city: Kingston
country: Canada
facility: Local Institution - 0127
state: Ontario
city: Oshawa
country: Canada
facility: Local Institution - 0078
state: Ontario
city: Chicoutimi
country: Canada
facility: Local Institution - 0237
state: Quebec
city: Rimouski
country: Canada
facility: Local Institution - 0070
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Local Institution - 0092
state: Quebec
city: Quebec
country: Canada
facility: Local Institution - 0126
city: Santiago
country: Chile
facility: Local Institution - 0041
state: Metropolitana
city: Vina del Mar
country: Chile
facility: Local Institution - 0040
state: Valparaiso
city: Beijing
country: China
facility: Local Institution - 0146
state: BEI
city: Chongqing
country: China
facility: Local Institution - 0149
state: Chongqing
city: Fuzhou
country: China
facility: Local Institution - 0179
state: Fujian
city: Xiamen
country: China
facility: Local Institution - 0164
state: Fujian
city: Guiyang
country: China
facility: Local Institution - 0192
state: Guizhou
city: Hankou
country: China
facility: Local Institution - 0147
state: Hubei
city: Wuhan
country: China
facility: Local Institution - 0148
state: Hubei
city: Wuhan
country: China
facility: Local Institution - 0150
state: Hubei
city: Changsha
country: China
facility: Local Institution - 0154
state: Hunan
city: Nanjing
country: China
facility: Local Institution - 0139
state: Jiangsu
city: Nanchang
country: China
facility: Local Institution - 0178
state: Jiangxi
city: Changchun
country: China
facility: Local Institution - 0170
state: Jilin
city: Changchun
country: China
facility: Local Institution - 0183
state: Jilin
city: Gongzhuling
country: China
facility: Local Institution - 0180
state: Jilin
city: Jinan
country: China
facility: Local Institution - 0138
state: Shandong
city: Shanghai
country: China
facility: Local Institution - 0145
state: Shanghai
city: Chengdu
country: China
facility: Local Institution - 0186
state: Sichuan
city: Chengdu
country: China
facility: Local Institution - 0189
state: Sichuan
city: Hangzhou
country: China
facility: Local Institution - 0140
state: Zhejiang
city: Linhai
country: China
facility: Local Institution - 0184
state: Zhejiang
city: Bordeaux
country: France
facility: Local Institution - 0086
city: Dijon
country: France
facility: Local Institution - 0087
city: Lyon
country: France
facility: Local Institution - 0081
city: Montpellier
country: France
facility: Local Institution - 0082
city: Nantes
country: France
facility: Local Institution - 0084
city: Paris Cedex 14
country: France
facility: Local Institution - 0090
city: Paris Cedex 5
country: France
facility: Local Institution - 0083
city: Paris
country: France
facility: Local Institution - 0227
city: Paris
country: France
facility: Local Institution - 0091
city: Tours Cedex 09
country: France
facility: Local Institution - 0089
city: Berlin
country: Germany
facility: Local Institution - 0060
city: Essen
country: Germany
facility: Local Institution - 0063
city: Grosshansdorf
country: Germany
facility: Local Institution - 0076
city: Hamm
country: Germany
facility: Local Institution - 0101
city: Heidelberg
country: Germany
facility: Local Institution - 0073
city: Immenhausen
country: Germany
facility: Local Institution - 0061
city: Kempten
country: Germany
facility: Local Institution - 0062
city: Loewenstein
country: Germany
facility: Local Institution - 0075
city: Mainz
country: Germany
facility: Local Institution - 0109
city: Stuttgart
country: Germany
facility: Local Institution - 0072
city: Athens
country: Greece
facility: Local Institution - 0161
city: Athens
country: Greece
facility: Local Institution - 0135
city: Larissa
country: Greece
facility: Local Institution - 0136
city: N.Kifissia
country: Greece
facility: Local Institution - 0162
city: Dublin 8
country: Ireland
facility: Local Institution - 0024
state: Dublin
city: Dublin
country: Ireland
facility: Local Institution - 0023
city: Brescia
country: Italy
facility: Local Institution - 0068
city: Catania
country: Italy
facility: Aou Policlinico V. Emanuele Di Catania
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero-Universitaria Mater Domini
city: Lucca
country: Italy
facility: Local Institution - 0050
city: Milano
country: Italy
facility: Local Institution - 0115
city: Monza (MB)
country: Italy
facility: Local Institution - 0114
city: Perugia
country: Italy
facility: Local Institution - 0048
city: Nagoya
country: Japan
facility: Local Institution - 0204
state: Aichi
city: Fukuoka-shi
country: Japan
facility: Local Institution - 0212
state: Fukuoka
city: Kurume-shi
country: Japan
facility: Local Institution - 0211
state: Fukuoka
city: Ota
country: Japan
facility: Local Institution - 0197
state: Gunma
city: Sapporo-shi
country: Japan
facility: Local Institution - 0195
state: Hokkaido
city: Kobe
country: Japan
facility: Local Institution - 0206
state: Hyogo
city: Kanazawa-shi
country: Japan
facility: Local Institution - 0203
state: Ishikawa
city: Yokohama-shi
country: Japan
facility: Local Institution - 0216
state: Kanagawa
city: Yokohama-Shi
country: Japan
facility: Local Institution - 0201
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution - 0217
state: Kanagawa
city: Sendai-shi
country: Japan
facility: Local Institution - 0196
state: Miyagi
city: Niigata-shi
country: Japan
facility: Local Institution - 0202
state: Niigata
city: Osaka-shi
country: Japan
facility: Local Institution - 0205
state: Osaka
city: Osakasayama
country: Japan
facility: Local Institution - 0210
state: Osaka
city: Hidaka-shi
country: Japan
facility: Local Institution - 0198
state: Saitama
city: Kitaadachi-gun
country: Japan
facility: Local Institution - 0174
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0199
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0200
state: Tokyo
city: Ube
country: Japan
facility: Local Institution - 0232
state: Yamaguchi
city: Wakayama
country: Japan
facility: Local Institution - 0175
city: Cheongju-si, Chungcheonbuk-do,
country: Korea, Republic of
facility: Local Institution - 0167
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0152
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0168
city: La Paz
country: Mexico
facility: Local Institution - 0027
state: BAJA Californa SUR
city: Df
country: Mexico
facility: Local Institution - 0067
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution - 0080
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 0014
state: Nuevo LEON
city: Culiacan
country: Mexico
facility: Local Institution - 0015
state: Sinaloa
city: Amsterdam
country: Netherlands
facility: Local Institution - 0006
city: Arnhem
country: Netherlands
facility: Local Institution - 0025
city: Leiden
country: Netherlands
facility: Local Institution - 0240
city: Maastrict
country: Netherlands
facility: Local Institution - 0005
city: Veldhoven
country: Netherlands
facility: Local Institution - 0026
city: Bydgoszcz
country: Poland
facility: Local Institution - 0107
city: Gdansk
country: Poland
facility: Local Institution - 0102
city: Krakow
country: Poland
facility: Local Institution - 0104
city: Tomaszow Mazowiecki
country: Poland
facility: Local Institution - 0235
city: Hato Rey
country: Puerto Rico
facility: Local Institution - 0120
city: San Juan
country: Puerto Rico
facility: GCM Medical Group, PSC - Hato Rey Site
city: Bucharest
country: Romania
facility: Local Institution - 0018
city: Bucuresti
country: Romania
facility: Local Institution - 0222
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0019
city: Constanta
country: Romania
facility: Local Institution - 0020
city: Craiova
country: Romania
facility: Local Institution - 0017
city: Floresti/ Cluj
country: Romania
facility: Local Institution - 0021
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution - 0171
city: Barcelona
country: Spain
facility: Local Institution - 0106
city: Hospitalet de Llobregat
country: Spain
facility: Local Institution - 0099
city: Madrid
country: Spain
facility: Local Institution - 0096
city: Madrid
country: Spain
facility: Local Institution - 0095
city: Pamplona
country: Spain
facility: Local Institution - 0098
city: Santiago de Compostela
country: Spain
facility: Local Institution - 0105
city: Sevilla
country: Spain
facility: Local Institution - 0097
city: Zaragoza
country: Spain
facility: Local Institution - 0100
city: Goteborg
country: Sweden
facility: Local Institution - 0065
state: Vastra Gotalands Lan
city: Stockholm
country: Sweden
facility: Local Institution - 0064
city: Basel
country: Switzerland
facility: Local Institution - 0057
city: Lausanne
country: Switzerland
facility: Local Institution - 0058
city: St.Gallen
country: Switzerland
facility: Local Institution - 0059
city: Zuerich
country: Switzerland
facility: Local Institution - 0056
city: KaohsiungCity
country: Taiwan
facility: Local Institution - 0208
city: New Taipei City
country: Taiwan
facility: Local Institution - 0214
city: Tainan
country: Taiwan
facility: Local Institution - 0209
city: Taipei City
country: Taiwan
facility: Local Institution - 0133
city: Taipei
country: Taiwan
facility: Local Institution - 0213
city: Taipei
country: Taiwan
facility: Local Institution - 0143
city: Poole
country: United Kingdom
facility: Local Institution - 0010
state: Dorset
city: Swansea
country: United Kingdom
facility: Local Institution - 0012
state: Glamorgan
city: Aberdeen
country: United Kingdom
facility: Local Institution - 0054
city: Bebington
country: United Kingdom
facility: Local Institution - 0007
city: Hull
country: United Kingdom
facility: Local Institution - 0009
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: De Ruysscher D, Ramalingam S, Urbanic J, Gerber DE, Tan DSW, Cai J, Li A, Peters S. CheckMate 73L: A Phase 3 Study Comparing Nivolumab Plus Concurrent Chemoradiotherapy Followed by Nivolumab With or Without Ipilimumab Versus Concurrent Chemoradiotherapy Followed by Durvalumab for Previously Untreated, Locally Advanced Stage III Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2022 May;23(3):e264-e268. doi: 10.1016/j.cllc.2021.07.005. Epub 2021 Jul 19.