NCT02477826 · CITED IN SOURCE DOCUMENTS

An Investigational Immuno-therapy Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2025-10-30

The purpose of this study is to show that Nivolumab, or Nivolumab plus Ipilimumab, or Nivolumab plus Platinum-Doublet Chemotherapy improves progression free survival and/or overall survival compared with chemotherapy in patients with advanced lung cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Progression-Free Survival Per BICR

→

outcome · POSTED

Overall Survival

→

outcome · POSTED

Objective Response Rate (ORR) Per BICR

→

outcome · POSTED

Percentage of Participants With Symptom Deterioration at Week 12 Assessed Via Lung Cancer Symptom Scale

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: * Subjects with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy * Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing, with results, performed by the central lab during the Screening period * 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 Exclusion Criteria: * Subjects with untreated Central nervous system (CNS) metastases are excluded * Subjects with an active, known or suspected autoimmune disease are excluded * Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) indicating acute or chronic infection Other protocol defined inclusion/exclusion criteria apply
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Nivolumab intravenously (IV) as specified
intervention Names
Drug: Nivolumab
label
Arm A: Nivolumab
type
EXPERIMENTAL
description
Nivolumab + Ipilimumab IV as specified
intervention Names
Drug: Nivolumab
Drug: Ipilimumab
label
Arm B: Nivolumab + Ipilimumab
type
EXPERIMENTAL
description
Nivolumab + Platinum doublet chemotherapy (IV) dose as specified
intervention Names
Drug: Nivolumab
Drug: Carboplatin
Drug: Cisplatin
Drug: Gemcitabine
Drug: Pemetrexed
Drug: Paclitaxel
label
Arm C: Nivolumab + Platinum doublet chemotherapy
type
EXPERIMENTAL
description
Chemotherapy administered on specified days of IV chemotherapy
intervention Names
Drug: Carboplatin
Drug: Cisplatin
Drug: Gemcitabine
Drug: Pemetrexed
Drug: Paclitaxel
label
Arm D: Platinum doublet chemotherapy
type
EXPERIMENTAL

interventions

arm Group Labels
Arm A: Nivolumab
Arm B: Nivolumab + Ipilimumab
Arm C: Nivolumab + Platinum doublet chemotherapy
name
Nivolumab
other Names
Opdivo
type
DRUG
arm Group Labels
Arm B: Nivolumab + Ipilimumab
name
Ipilimumab
other Names
Yervoy
type
DRUG
arm Group Labels
Arm C: Nivolumab + Platinum doublet chemotherapy
Arm D: Platinum doublet chemotherapy
name
Carboplatin
type
DRUG
arm Group Labels
Arm C: Nivolumab + Platinum doublet chemotherapy
Arm D: Platinum doublet chemotherapy
name
Cisplatin
type
DRUG
arm Group Labels
Arm C: Nivolumab + Platinum doublet chemotherapy
Arm D: Platinum doublet chemotherapy
name
Gemcitabine
type
DRUG
arm Group Labels
Arm C: Nivolumab + Platinum doublet chemotherapy
Arm D: Platinum doublet chemotherapy
name
Pemetrexed
type
DRUG
arm Group Labels
Arm C: Nivolumab + Platinum doublet chemotherapy
Arm D: Platinum doublet chemotherapy
name
Paclitaxel
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 2747
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first based on Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
measure
Progression-Free Survival Per BICR
time Frame
From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)
description
OS for all randomized participants is the time between randomization date and the date of death from any cause.
measure
Overall Survival
time Frame
From randomization untill death or last follow up whichever occurs first (up to approximately 481 weeks)

secondary Outcomes

description
Objective response rate (ORR) is defined as the number of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure
Objective Response Rate (ORR) Per BICR
time Frame
From randomization untill disease progression or death, whichever occurs first (up to approximately 481 weeks)
description
The Lung Cancer Symptom Scale (LCSS) is a disease measure of quality of life which evaluates six major lung cancer symptoms and their effect on overall distress and symptom severity, impact on day-to-day activities, and overall quality of life. This patient reported outcome (PRO) questionnaire assesses the following 6 symptoms items (appetite loss, fatigue, cough, dyspnea, hemoptysis, pain) and 3 summary global items (symptom distress, activity level, overall quality of life) for patients using visual analogue scales (VAS) (100 mm horizontal line) ranging from 0 (best rating) to 100 (worst rating). The LCSS average total score is sum of items 1 to 9 divided by the total number of items ((sum of items 1 to 9)/9) ranging from 0 to 100 where high score represent worst outcome. Disease-Related Symptom Deterioration by Week 12 defined as a 10 points or more increase from baseline in LCSS average score at any time (on or off-treatment) up to 95 days from randomization date.
measure
Percentage of Participants With Symptom Deterioration at Week 12 Assessed Via Lung Cancer Symptom Scale
time Frame
Week 12

Full study description

brief Summary: The purpose of this study is to show that Nivolumab, or Nivolumab plus Ipilimumab, or Nivolumab plus Platinum-Doublet Chemotherapy improves progression free survival and/or overall survival compared with chemotherapy in patients with advanced lung cancer.

Source references

references

citation
Nishio M, Hayashi H, Goto Y, Ikeda S, Yokoyama T, Tanaka H, Tambo Y, Hotta K, Fukuhara T, Daga H, Masubuchi K, Aoyama T, Tschaika M, Hu N, Mizutani H. Nivolumab plus ipilimumab-based treatment in Japanese patients with metastatic non-small cell lung cancer and tumor PD-L1 < 1%: a pooled analysis. Int J Clin Oncol. 2026 Aug 11. doi: 10.1007/s10147-026-03116-w. Online ahead of print.
pmid
42579028
type
DERIVED
citation
Peters S, Paz-Ares LG, Reck M, Carbone DP, Brahmer JR, Borghaei H, Lu S, O'Byrne KJ, John T, Ciuleanu TE, Schenker M, Bernabe Caro R, Nishio M, Cobo M, Lee JS, Zurawski B, Pluzanski A, Aoyama T, Tschaika M, Devas V, Grootendorst DJ, Ramalingam SS. Long-Term Survival Outcomes With First-Line Nivolumab Plus Ipilimumab-Based Treatment in Patients With Metastatic NSCLC and Tumor Programmed Death-Ligand 1 Lower Than 1%: A Pooled Analysis. J Thorac Oncol. 2025 Jan;20(1):94-108. doi: 10.1016/j.jtho.2024.09.1439. Epub 2024 Oct 4.
pmid
39369790
type
DERIVED
citation
Mason M, Lapuente-Santana O, Halkola AS, Wang W, Mall R, Xiao X, Kaufman J, Fu J, Pfeil J, Banerjee J, Chung V, Chang H, Chasalow SD, Lin HY, Chai R, Yu T, Finotello F, Mirtti T, Mayranpaa MI, Bao J, Verschuren EW, Ahmed EI, Ceccarelli M, Miller LD, Monaco G, Hendrickx WRL, Sherif S, Yang L, Tang M, Gu SS, Zhang W, Zhang Y, Zeng Z, Das Sahu A, Liu Y, Yang W, Bedognetti D, Tang J, Eduati F, Laajala TD, Geese WJ, Guinney J, Szustakowski JD, Vincent BG, Carbone DP. A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer. J Transl Med. 2024 Feb 21;22(1):190. doi: 10.1186/s12967-023-04705-3.
pmid
38383458
type
DERIVED
citation
Brahmer JR, Lee JS, Ciuleanu TE, Bernabe Caro R, Nishio M, Urban L, Audigier-Valette C, Lupinacci L, Sangha R, Pluzanski A, Burgers J, Mahave M, Ahmed S, Schoenfeld AJ, Paz-Ares LG, Reck M, Borghaei H, O'Byrne KJ, Gupta RG, Bushong J, Li L, Blum SI, Eccles LJ, Ramalingam SS. Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227. J Clin Oncol. 2023 Feb 20;41(6):1200-1212. doi: 10.1200/JCO.22.01503. Epub 2022 Oct 12.
pmid
36223558
type
DERIVED
citation
Reck M, Ciuleanu TE, Lee JS, Schenker M, Audigier-Valette C, Zurawski B, Linardou H, Otterson GA, Salman P, Nishio M, de la Mora Jimenez E, Lesniewski-Kmak K, Albert I, Ahmed S, Syrigos K, Penrod JR, Yuan Y, Blum SI, Nathan FE, Sun X, Moreno-Koehler A, Taylor F, O'Byrne KJ. First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1. J Thorac Oncol. 2021 Apr;16(4):665-676. doi: 10.1016/j.jtho.2020.12.019. Epub 2021 Jan 21.
pmid
33485960
type
DERIVED
citation
Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. doi: 10.1056/NEJMoa1910231. Epub 2019 Sep 28.
pmid
31562796
type
DERIVED
citation
Reck M, Schenker M, Lee KH, Provencio M, Nishio M, Lesniewski-Kmak K, Sangha R, Ahmed S, Raimbourg J, Feeney K, Corre R, Franke FA, Richardet E, Penrod JR, Yuan Y, Nathan FE, Bhagavatheeswaran P, DeRosa M, Taylor F, Lawrance R, Brahmer J. Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial. Eur J Cancer. 2019 Jul;116:137-147. doi: 10.1016/j.ejca.2019.05.008. Epub 2019 Jun 11.
pmid
31195357
type
DERIVED
citation
Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018 May 31;378(22):2093-2104. doi: 10.1056/NEJMoa1801946. Epub 2018 Apr 16.
pmid
29658845
type
DERIVED