A Study of Nivolumab and Ipilimumab Combined With Chemotherapy Compared to Chemotherapy Alone in First Line NSCLC
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03215706
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine whether Nivolumab, Ipilimumab combined with chemotherapy is more effective than chemotherapy by itself when treating stage IV NSCLC as the first treatment given for the disease
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 719
- Participants with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
- Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria
- Participants must have PD-L1 IHC testing with results performed by a central laboratory during the screening period
- Participants with known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded
- Participants with known anaplastic lymphoma kinase (ALK) translocations which are sensitive to available targeted inhibitor therapy are excluded
- Participants with untreated CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment
Other protocol inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Module A Nivolumab Chemotherapy/Biologics combined Module A Carboplatin Chemotherapy/Biologics combined Module A Ipilimumab Chemotherapy/Biologics combined Module A Paclitaxel Chemotherapy/Biologics combined Module A Pemetrexed Chemotherapy/Biologics combined Module A Cisplatin Chemotherapy/Biologics combined Module B Paclitaxel Chemotherapy Combination Module B Carboplatin Chemotherapy Combination Module B Pemetrexed Chemotherapy Combination Module B Cisplatin Chemotherapy Combination
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From date of randomization to date of death (assessed up to October 2019, approximately 23 months) OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) by BICR From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2019, approximately 23 months) PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
Objective Response Rate (ORR) by BICR From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months) ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression.
Duration of Response (DoR) From date of first confirmed response to date of tumor progression (assessed up to October 2019, approximately 23 months) DoR was defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented BICR-assessed tumor progression (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who started subsequent therapy (including palliative local therapy) without a prior reported progression were censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy (including palliative local therapy). Participants who died without a reported prior progression were considered to have progressed on the date of their death. For subjects who neither progressed nor died, DoR was censored on the date of their last evaluable tumor assessment. DoR was evaluated for responders (confirmed CR or PR) only.
Time to Response (TTR) From date of randomization to date of first confirmed documented response (assessed up to October 2019, approximately 23 months) TTR was defined as the time from randomization to the date of the first confirmed documented response (CR or PR), as assessed by the BICR. TTR was evaluated for responders (confirmed CR or PR) only.
Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months) PD-L1 expression was defined as the percent of tumor cells with membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC 28-8 pharmDx test. PD-L1 expression was classified as PD-L1 ≥1% (≥1% tumor cells with membrane staining in a minimum of a hundred evaluable tumor cells), PD-L1 \< 1% and PD-L1 not quantifiable (without quantifiable PD-L1 expression), PD-L1 expression ≥ 50%, PD-L1 expression 1 to 49%
PFS by BICR by PD-L1 Tumor Cell Expression From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2019, approximately 23 months) PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
OS by PD-L1 Tumor Cell Expression From date of randomization to date of death (assessed up to October 2019, approximately 23 months) OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
Trial Locations
- Locations (116)
Local Institution - 0091
🇺🇸Wichita, Kansas, United States
Local Institution - 0004
🇺🇸Lexington, Kentucky, United States
Local Institution - 0086
🇦🇺Gosford, New South Wales, Australia
Local Institution - 0082
🇨🇦Montreal, Quebec, Canada
Local Institution - 0080
🇨🇦Rimouski, Quebec, Canada
Local Institution - 0084
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0115
🇯🇵Kanazawa-shi, Ishikawa, Japan
Local Institution - 0100
🇯🇵Shiwa-gun, Iwate, Japan
Local Institution - 0129
🇯🇵Yokohama-shi, Kanagawa, Japan
Local Institution - 0055
🇪🇸Malaga, Spain
Local Institution - 0108
🇨🇳Xi'an City, Shan3xi, China
Local Institution - 0110
🇨🇳Hangzhou, Zhejiang, China
Local Institution - 0111
🇨🇳Zhejiang, Zhejiang, China
Local Institution - 0113
🇨🇳Beijing, China
Local Institution - 0112
🇨🇳Shanghai, China
Local Institution - 0010
🇫🇷Bron, Rhone Alpes, France
Local Institution - 0009
🇫🇷Lyon Cedex08, Rhône-Alpes, France
Local Institution - 0013
🇫🇷Caen, France
Local Institution - 0087
🇵🇱Bydgoszcz, Poland
Local Institution - 0022
🇵🇱Bytom, Poland
Local Institution - 0085
🇵🇱Gdańsk, Poland
Local Institution - 0034
🇷🇴Bucharest, Romania
Local Institution - 0031
🇷🇴Cluj Napoca, Romania
Local Institution - 0032
🇷🇴Craiova, Romania
Local Institution - 0024
🇷🇺Moscow, Russian Federation
Local Institution - 0025
🇷🇺St.petersburg, Russian Federation
Local Institution - 0054
🇪🇸A Coruña, Spain
Local Institution - 0053
🇪🇸Barcelona, Spain
Local Institution - 0052
🇪🇸Madrid, Spain
Memorial Health Systems
🇺🇸Colorado Springs, Colorado, United States
Local Institution - 0044
🇺🇸Plainville, Connecticut, United States
Local Institution - 0045
🇺🇸Jacksonville, Florida, United States
Local Institution - 0029
🇺🇸Marietta, Georgia, United States
Local Institution - 0105
🇺🇸Detroit, Michigan, United States
Local Institution - 0058
🇺🇸Johnson City, New York, United States
Local Institution - 0098
🇺🇸Mineola, New York, United States
Local Institution - 0095
🇺🇸Columbus, Ohio, United States
Local Institution - 0006
🇺🇸Lancaster, Pennsylvania, United States
Local Institution - 0047
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 0093
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 0094
🇺🇸Charleston, South Carolina, United States
Southwest Regional Cancer Clinic
🇺🇸Saint George, Utah, United States
Local Institution - 0099
🇺🇸Madison, Wisconsin, United States
Local Institution - 0014
🇦🇷Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Local Institution - 0028
🇦🇷Rio Cuarto, Cordoba, Argentina
Local Institution - 0026
🇦🇷Viedma, Rio Negro, Argentina
Local Institution - 0027
🇦🇷Rosario, Santa Fe, Argentina
Local Institution - 0030
🇦🇷Cordoba, Argentina
Local Institution - 0040
🇦🇺Bedford Park, South Australia, Australia
Local Institution - 0089
🇦🇺Box Hill, Victoria, Australia
Local Institution - 0036
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0078
🇦🇺Murdoch, Western Australia, Australia
Local Institution - 0002
🇧🇪Gilly, Belgium
Local Institution - 0033
🇧🇪Leuven, Belgium
Local Institution - 0001
🇧🇪Roeselare, Belgium
Local Institution - 0068
🇧🇷Natal, RIO Grande DO Norte, Brazil
Local Institution - 0063
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Local Institution - 0067
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Local Institution - 0069
🇧🇷Blumenau, Santa Catarina, Brazil
Local Institution - 0064
🇧🇷Barretos, Sao Paulo, Brazil
Local Institution - 0065
🇧🇷Sao Jose Do Rio Preto, Sao Paulo, Brazil
Local Institution - 0066
🇧🇷Rio De Janeiro, Brazil
Local Institution - 0070
🇧🇷São Paulo, Brazil
Local Institution - 0090
🇨🇦Montreal, Quebec, Canada
Local Institution - 0083
🇨🇦Montreal, Quebec, Canada
Local Institution - 0059
🇨🇱Santiago, Región Metropolitana De Santiago, Chile
Local Institution - 0079
🇨🇱Vina Del Mar, Valparaiso, Chile
Local Institution - 0139
🇨🇳Beijing, BEI, China
Local Institution - 0146
🇨🇳Haikou, Hainan, China
Local Institution - 0148
🇨🇳Zhengzhou, Henan, China
Local Institution - 0120
🇨🇳Zhengzhou, Henan, China
Local Institution - 0144
🇨🇳Changsha, Hunan, China
Local Institution - 0106
🇨🇳Changchun, Jilin, China
Local Institution - 0071
🇫🇷Lille Cedex, France
Local Institution - 0012
🇫🇷Montpellier, France
Local Institution - 0035
🇫🇷Nantes, France
Local Institution - 0011
🇫🇷Paris Cedex 20, France
Local Institution - 0097
🇫🇷Saint-Brieuc, France
Local Institution - 0073
🇩🇪Berlin, Germany
Local Institution - 0016
🇩🇪Gauting, Germany
Local Institution - 0072
🇩🇪Grosshansdorf, Germany
Local Institution - 0019
🇩🇪Hemer, Germany
Local Institution - 0017
🇩🇪Immenhausen, Germany
Local Institution - 0074
🇩🇪Magdeburg, Germany
Local Institution - 0015
🇩🇪Muenchen, Germany
Local Institution - 0018
🇩🇪Stuttgart, Germany
Local Institution - 0021
🇮🇪Dublin, Ireland
Local Institution - 0020
🇮🇪Limerick, Ireland
Local Institution - 0042
🇮🇹Lucca, Italy
Local Institution - 0041
🇮🇹Milano, Italy
Local Institution - 0043
🇮🇹Napoli, Italy
Local Institution - 0101
🇯🇵Fukushima-shi, Fukushima, Japan
Local Institution - 0118
🇯🇵Maebashi-shi, Gunma, Japan
Local Institution - 0128
🇯🇵Ota-shi, Gunma, Japan
Local Institution - 0138
🇯🇵Hiroshima-shi, Hiroshima, Japan
Local Institution - 0137
🇯🇵Hiroshima-shi, Hiroshima, Japan
Local Institution - 0127
🇯🇵Sapporo-shi, Hokkaido, Japan
Local Institution - 0131
🇯🇵Akashi-shi, Hyogo, Japan
Local Institution - 0119
🇯🇵Himeji-shi, Hyogo, Japan
Local Institution - 0104
🇯🇵Kobe-shi, Hyogo, Japan
Local Institution - 0114
🇯🇵Yokohama-Shi, Kanagawa, Japan
Local Institution - 0134
🇯🇵Yokohama-shi, Kanagawa, Japan
Local Institution - 0116
🇯🇵Niigata-shi, Niigata, Japan
Local Institution - 0136
🇯🇵Okayama-shi, Okayama, Japan
Local Institution - 0135
🇯🇵Habikino-shi, Osaka, Japan
Local Institution - 0103
🇯🇵Osaka-Sayama, Osaka, Japan
Local Institution - 0102
🇯🇵Kitaadachi-gun, Saitama, Japan
Local Institution - 0132
🇯🇵Ube-shi, Yamaguchi, Japan
Local Institution - 0130
🇯🇵Osaka, Japan
Local Institution - 0077
🇲🇽La Paz, BAJA Californa SUR, Mexico
Local Institution - 0061
🇲🇽Guadalajara, Jalisco, Mexico
Local Institution - 0075
🇲🇽Veracruz, Veracruz, Mexico
Local Institution - 0056
🇪🇸Valencia, Spain
Local Institution - 0050
🇬🇧Guildford, United Kingdom
Local Institution - 0049
🇬🇧London, United Kingdom
Local Institution - 0048
🇬🇧Tauton, United Kingdom