An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026)
- Conditions
- Stage IV or Recurrent Non-Small Cell Lung Cancer
- Interventions
- Biological: NivolumabDrug: GemcitabineDrug: CisplatinDrug: CarboplatinDrug: PaclitaxelDrug: Pemetrexed
- Registration Number
- NCT02041533
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to show that Nivolumab will improve progression free survival in subjects with strongly Stage IV or Recurrent PD-L1+ non-small cell lung cancer when compared to chemotherapy
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 541
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1
- Histologically confirmed Stage IV, or Recurrent NSCLC with no prior systemic anticancer therapy
- Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria
- PD-L1+ on immunohistochemistry testing performed by central lab
- Men and women, ages ≥ 18 years of age
- Known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy
- Known anaplastic lymphoma kinase (ALK) translocations
- Untreated central nervous system (CNS) metastases
- Previous malignancies
- Active, known or suspected autoimmune disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Nivolumab subjects Nivolumab Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure Arm B: Investigator's Choice Chemotherapy Nivolumab Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first Squamous subjects: * Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or * Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or * Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle Non-Squamous subjects: * Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle * Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle Optional crossover: * Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure Arm B: Investigator's Choice Chemotherapy Gemcitabine Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first Squamous subjects: * Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or * Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or * Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle Non-Squamous subjects: * Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle * Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle Optional crossover: * Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure Arm B: Investigator's Choice Chemotherapy Carboplatin Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first Squamous subjects: * Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or * Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or * Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle Non-Squamous subjects: * Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle * Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle Optional crossover: * Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure Arm B: Investigator's Choice Chemotherapy Cisplatin Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first Squamous subjects: * Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or * Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or * Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle Non-Squamous subjects: * Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle * Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle Optional crossover: * Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure Arm B: Investigator's Choice Chemotherapy Pemetrexed Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first Squamous subjects: * Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or * Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or * Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle Non-Squamous subjects: * Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle * Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle Optional crossover: * Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure Arm B: Investigator's Choice Chemotherapy Paclitaxel Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first Squamous subjects: * Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or * Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or * Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle Non-Squamous subjects: * Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle * Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle Optional crossover: * Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure
- Primary Outcome Measures
Name Time Method Progression-Free Survival in Participants With PD-L1 Expression >= 5% From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months) Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die 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 day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival in All Randomized Participants From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months) Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die 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 day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.
Overall Survival in Participants With PD-L1 Expression >= 5% From date of randomization to date of death (up to approximately 89 months) Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.
Overall Survival in All Randomized Participants From date of randomization to date of death (up to approximately 89 months) Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.
Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5% From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to August 2016, approximately 28 months) ORR was defined as the proportion of randomized participants who achieved a Best Overall Response (BOR) of CR or PR using the RECIST v1.1 criteria per Independent Radiology Review Committee (IRRC) assessment. BOR was defined as the best response designation recorded between the date of randomization and the date of objectively documented progression or start of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. For participants who continued treatment beyond progression, BOR was determined from response designations recorded up to the time of initial progression. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by \>=50% of previously involved sites from nadir.
Disease-related Symptom Improvement Rate by Week 12 From date of randomization to week 12 The Lung Cancer Symptom Score (LCSS) is a validated instrument designed to assess the impact of treatment on disease-related symptoms. It consists of 6 symptom-specific questions related to dyspnea, cough, fatigue, pain, hemoptysis and anorexia plus 3 summary items: symptom distress, interference with activity, and global HRQoL. The degree of impairment was recorded on a 100 mm visual analogue scale with scores from 0 to 100 with zero representing the best score. Disease-related symptom improvement rate by Week 12 is defined as the proportion of all randomized (all PD-L1+) participants who had 10 points or more decrease from baseline in average symptom burden index score at any time between randomization and Week 12.
Trial Locations
- Locations (141)
Local Institution - 0159
🇯🇵Akashi, Hyogo, Japan
Southern Cancer Center, Inc.
🇺🇸Mobile, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Local Institution - 0037
🇺🇸Chicago, Illinois, United States
Local Institution - 0027
🇺🇸Columbus, Ohio, United States
Local Institution - 0054
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0002
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0018
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 0006
🇺🇸Dallas, Texas, United States
Local Institution - 0072
🇦🇺Fitzroy, Victoria, Australia
Local Institution - 0113
🇨🇦Toronto, Ontario, Canada
Local Institution - 0130
🇹🇷Kayseri, Turkey
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Local Institution - 0033
🇺🇸Ocala, Florida, United States
Crescent City Research Consortium, LLC
🇺🇸Marrero, Louisiana, United States
Local Institution - 0011
🇺🇸Charleston, South Carolina, United States
Local Institution - 0038
🇺🇸Greenville, South Carolina, United States
Local Institution - 0034
🇺🇸Tucson, Arizona, United States
University Of Colorado Hosp
🇺🇸Aurora, Colorado, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Local Institution - 0062
🇧🇪Leuven, Belgium
Local Institution - 0016
🇺🇸Stanford, California, United States
Local Institution - 0010
🇺🇸Atlanta, Georgia, United States
Local Institution - 0020
🇺🇸New Haven, Connecticut, United States
Local Institution - 0104
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0094
🇭🇺Matrahaza, Hungary
Local Institution - 0063
🇩🇪Koeln, Germany
Local Institution - 0052
🇦🇷Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina
Local Institution - 0105
🇫🇷Lille, France
Local Institution - 0044
🇧🇪Brussels, Belgium
Local Institution - 0055
🇧🇪Edegem, Belgium
Local Institution - 0058
🇨🇿Praha 8, Czechia
Local Institution - 0049
🇦🇷Capital Federal, Buenos Aires, Argentina
Local Institution - 0109
🇨🇦Rimouski, Quebec, Canada
Local Institution - 0003
🇺🇸Durham, North Carolina, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Local Institution - 0005
🇺🇸New York, New York, United States
Local Institution - 0051
🇦🇷Berazategui, Buenos Aires, Argentina
Local Institution - 0060
🇨🇿Usti nad Labem, Czechia
Local Institution - 0056
🇧🇪Gent, Belgium
Local Institution - 0059
🇨🇿Olomouc, Czechia
Local Institution - 0064
🇩🇪Heidelberg, Germany
Local Institution - 0048
🇦🇷Cordoba, Argentina
Local Institution - 0135
🇧🇷Barretos, Sao Paulo, Brazil
Local Institution - 0140
🇫🇷Strasbourg, France
Local Institution - 0118
🇫🇮Vaasa, Finland
Local Institution - 0102
🇫🇷Marseille Cedex 20, France
Local Institution - 0061
🇨🇿Ostrava - Poruba, Czechia
Local Institution - 0100
🇫🇷Rennes Cedex 9, France
Local Institution - 0073
🇬🇷Heraklion, Creta, Greece
Local Institution - 0110
🇨🇦Montreal, Quebec, Canada
Local Institution - 0116
🇭🇺Debrecen, Hungary
Local Institution - 0167
🇫🇷Pontoise Cedex, France
Local Institution - 0066
🇩🇪Stuttgart, Germany
Local Institution - 0123
🇫🇷Caen, France
Local Institution - 0127
🇸🇪Stockholm, Sweden
Local Institution - 0039
🇪🇸Sevilla, Spain
Local Institution - 0097
🇬🇧Manchester, Greater Manchester, United Kingdom
Local Institution - 0053
🇬🇧Leeds, Yorkshire, United Kingdom
Local Institution - 0024
🇺🇸Baltimore, Maryland, United States
Local Institution - 0030
🇺🇸Miami, Florida, United States
Local Institution - 0036
🇺🇸Boston, Massachusetts, United States
Local Institution - 0023
🇺🇸Houston, Texas, United States
Local Institution - 0070
🇺🇸Boston, Massachusetts, United States
Local Institution - 0075
🇬🇷Athens, Greece
Local Institution - 0133
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Local Institution - 0087
🇦🇹Wien, Austria
Local Institution - 0120
🇫🇮Helsinki, Finland
Local Institution - 0122
🇲🇽Guadalajara, Jalisco, Mexico
Local Institution - 0069
🇷🇴Ploiesti, Romania
Local Institution - 0077
🇨🇭Lausanne, Switzerland
Local Institution - 0088
🇦🇹Wels, Austria
Local Institution - 0154
🇯🇵Chuo-ku, Tokyo, Japan
Local Institution - 0090
🇦🇺Camperdown, New South Wales, Australia
Northwest Georgia Oncology Center, P.C.
🇺🇸Marietta, Georgia, United States
Local Institution - 0007
🇺🇸Allentown, Pennsylvania, United States
Local Institution - 0008
🇺🇸Nashville, Tennessee, United States
Local Institution - 0029
🇺🇸Yakima, Washington, United States
Local Institution - 0086
🇨🇦Calgary, Alberta, Canada
Local Institution - 0163
🇰🇷Seoul, Korea, Republic of
Local Institution - 0098
🇬🇧London, Greater London, United Kingdom
Local Institution - 0014
🇺🇸Lexington, Kentucky, United States
Local Institution - 0009
🇺🇸New York, New York, United States
University Of North Carolina At Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Local Institution - 0012
🇺🇸Cleveland, Ohio, United States
Cancer Centers of South Texas
🇺🇸San Antonio, Texas, United States
Local Institution - 0050
🇦🇷Cordoba, Argentina
Local Institution - 0091
🇦🇺Brisbane, Queensland, Australia
Local Institution - 0071
🇦🇺Elizabeth Vale, South Australia, Australia
Local Institution - 0119
🇫🇮Tampere, Finland
Local Institution - 0134
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Local Institution - 0115
🇨🇦Hamilton, Ontario, Canada
Local Institution - 0074
🇩🇪Bamberg, Germany
Local Institution - 0065
🇩🇪Grosshansdorf, Germany
Local Institution - 0092
🇩🇪Wiesbaden, Germany
Local Institution - 0126
🇭🇺Budapest, Hungary
Local Institution - 0084
🇮🇹Avellino, Italy
Local Institution - 0142
🇮🇹Napoli, Italy
Local Institution - 0079
🇮🇹Livorno, Italy
Local Institution - 0143
🇮🇹Milano, Italy
Local Institution - 0153
🇯🇵Kobe City, Hyogo, Japan
Local Institution - 0151
🇯🇵Niigata-shi, Niigata, Japan
Local Institution - 0161
🇯🇵Nagoya-shi, Aichi, Japan
Local Institution - 0146
🇯🇵Nagoya, Aichi, Japan
Local Institution - 0082
🇮🇹Terni, Italy
Local Institution - 0148
🇯🇵Matsuyama-shi, Ehime, Japan
Local Institution - 0083
🇮🇹Perugia, Italy
Local Institution - 0144
🇯🇵Natori-shi, Miyagi, Japan
Local Institution - 0147
🇯🇵Miyakojima-ku, Osaka, Japan
Local Institution - 0150
🇯🇵Kitaadachi-gun, Saitama, Japan
Local Institution - 0166
🇯🇵Habikino-shi, Osaka, Japan
Local Institution - 0145
🇯🇵Osaka-sayama, Osaka, Japan
Local Institution - 0152
🇯🇵Sakai, Osaka, Japan
Local Institution - 0149
🇯🇵Sunto-gun, Shizuoka, Japan
Local Institution - 0165
🇯🇵Sapporo, Hokkaido, Japan
Local Institution - 0162
🇯🇵Ota, Gunma, Japan
Local Institution - 0160
🇯🇵Tokyo, Japan
Local Institution - 0158
🇯🇵Wakayama, Japan
Local Institution - 0155
🇰🇷Gangnam-gu, Korea, Republic of
Local Institution - 0164
🇰🇷Seoul, Korea, Republic of
Local Institution - 0117
🇲🇽Mexico, Distrito Federal, Mexico
Local Institution - 0124
🇲🇽Merida, Yucatan, Mexico
Local Institution - 0045
🇳🇱Amsterdam, Netherlands
Local Institution - 0057
🇳🇱Groningen, Netherlands
Local Institution - 0046
🇳🇱Rotterdam, Netherlands
Local Institution - 0114
🇵🇱Bydgoszcz, Poland
Local Institution - 0089
🇵🇱Warszawa, Poland
Local Institution - 0139
🇵🇱Lodz, Poland
Local Institution - 0131
🇵🇱Krakow, Poland
Local Institution - 0093
🇵🇱Wodzislaw Slaski, Poland
Local Institution - 0067
🇷🇴Cluj-napoca, Romania
Local Institution - 0068
🇷🇴Cluj Napoca, Romania
Local Institution - 0040
🇪🇸Barcelona, Spain
Local Institution - 0042
🇪🇸Malaga, Spain
Local Institution - 0041
🇪🇸Las Palmas De Gran Canaria, Spain
Local Institution - 0043
🇪🇸Valencia, Spain
Local Institution - 0047
🇪🇸Madrid, Spain
Local Institution - 0125
🇸🇪Uppsala, Sweden
Local Institution - 0076
🇨🇭Chur, Switzerland
Local Institution - 0078
🇨🇭Zuerich, Switzerland
Local Institution - 0157
🇨🇳Taipei, Taiwan