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) (CheckMate 227)

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Nivolumab; Drug: Ipilimumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemetrexed; Drug: Paclitaxel	Phase 3

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	2220 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)
Study Start Date :	August 2015
Estimated Primary Completion Date :	January 2019
Estimated Study Completion Date :	December 2020

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Arm A: Nivolumab; Nivolumab intravenously (IV) as specified	Drug: Nivolumab; Other Name: Opdivo
Experimental: Arm B: Nivolumab + Ipilimumab; Nivolumab + Ipilimumab IV as specified	Drug: Nivolumab; Other Name: Opdivo Drug: Ipilimumab; Other Name: Yervoy
Experimental: Arm C: Nivolumab + Platinum doublet chemotherapy; Nivolumab + Platinum doublet chemotherapy (IV) dose as specified	Drug: Nivolumab; Other Name: Opdivo Drug: Carboplatin Drug: Cisplatin Drug: Gemcitabine Drug: Pemetrexed Drug: Paclitaxel
Active Comparator: Arm D: Platinum doublet chemotherapy; Chemotherapy administered on specified days of IV chemotherapy.	Drug: Carboplatin Drug: Cisplatin Drug: Gemcitabine Drug: Pemetrexed Drug: Paclitaxel

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Overall survival (OS) [ Time Frame: approximately 48 months ]
2. Progression-free Survival (PFS) as determined by blinded independent central review (BICR) [ Time Frame: approximately 40 months ]

Secondary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: Up to 48 months ]
   ORR of nivolumab monotherapy and nivolumab in combination with ipilimumab to platinum-doublet chemotherapy in subjects with advanced lung cancer
2. Disease related symptom improvement as measured by the Lung Cancer Symptom Score (LCSS) in all subjects [ Time Frame: Up to 48 months ]
   Disease related symptom improvement assessed at each dosing for 6 months, then every 6 weeks while on treatment

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

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 could apply

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email:		Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 267 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Ono Pharmaceutical Co. Ltd

Investigators

Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

BMS Clinical Trial Information 

BMS clinical trial educational resource 

Investigator Inquiry form 

FDA Safety Alerts and Recalls 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 Apr 16. doi: 10.1056/NEJMoa1801946. [Epub ahead of print]

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02477826 History of Changes
Other Study ID Numbers:	CA209-227; 2014-003630-23 ( EudraCT Number )
First Posted:	June 23, 2015
Last Update Posted:	February 13, 2018
Last Verified:	February 2018

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Gemcitabine; Pemetrexed; Nivolumab; Carboplatin	Antibodies, Monoclonal; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors