A Neoadjuvant Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Versus Chemotherapy Alone in Early Stage Non-Small Cell Lung Cancer (NSCLC) (CheckMate 816)

January 2, 2026 updated by: Bristol-Myers Squibb

Randomized, OpenLabel, Phase 3 Trial of Nivolumab Plus Ipilimumab or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Early Stage NSCLC

The purpose of this neoadjuvant study is to compare nivolumab plus chemotherapy and chemotherapy alone in terms of safety and effectiveness, and to describe nivolumab plus ipilimumab's safety and effectiveness in treating resectable NSCLC.

This study has multiple primary endpoints.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

505

Phase

  • Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • Capital Federal, Buenos Aires, Argentina, 1426
        • Local Institution - 0022
      • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, 1181
        • Local Institution - 0023
  • Brazil
      • Rio de Janeiro, Brazil, 22793-080
        • Local Institution - 0075
    • Federal District
      • Brasília, Federal District, Brazil, 70200-730
        • Local Institution - 0079
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30130-090
        • Local Institution - 0077
    • Rio Grande do Sul
      • Ijuí, Rio Grande do Sul, Brazil, 98700-000
        • Local Institution - 0076
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Local Institution - 0073
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Fundacao Pio Xii Hosp Cancer De Barretos
  • Canada
    • Quebec
      • Gatineau, Quebec, Canada, J8P 7H2
        • Local Institution - 0095
      • Montreal, Quebec, Canada, H2X 0A9
        • Local Institution - 0138
      • Montreal, Quebec, Canada, H4A 3J1
        • Local Institution - 0017
      • Trois-Rivières, Quebec, Canada, G8Z 3R9
        • Local Institution - 0052
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Local Institution - 0016
  • China
      • Shanghai, China, 200030
        • Local Institution - 0165
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100142
        • Local Institution - 0161
      • Beijing, Beijing Municipality, China, 100730
        • Local Institution
      • Beijing, Beijing Municipality, China, 100853
        • Local Institution - 0156
    • Guangdong
      • Guangzhou, Guangdong, China, 510095
        • Local Institution - 0190
    • Hunan
      • Changsha, Hunan, China, 410008
        • Local Institution - 0192
      • Changsha, Hunan, China, 410013
        • Local Institution - 0175
      • Changsha, Hunan, China, 410013
        • Local Institution - 0193
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • Local Institution - 0179
      • Nanchang, Jiangxi, China, 330200
        • Local Institution - 0166
    • Jilin
      • Changchun, Jilin, China, 130012
        • Local Institution
    • Shan1xi
      • Xi'an, Shan1xi, China, 710061
        • Local Institution - 0159
    • Shan3xi
      • Xi'an, Shan3xi, China, 710038
        • Local Institution - 0180
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Local Institution - 0160
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Local Institution - 0178
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300060
        • Local Institution - 0163
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • Local Institution - 0189
      • Hangzhou, Zhejiang, China, 310016
        • Local Institution - 0183
      • Hangzhou, Zhejiang, China, 310022
        • Local Institution - 0182
  • France
      • Marseille, France, 13915
        • Local Institution - 0059
      • Paris, France, 75018
        • Local Institution - 0060
      • Paris, France, 75248
        • Local Institution - 0112
      • Pierre Benite Cedax, France, 69495
        • Local Institution - 0064
      • Rennes, France, 35033
        • Local Institution - 0061
      • Strasbourg, France, 67100
        • Local Institution - 0113
      • Toulouse, France, 31059
        • Local Institution - 0058
      • Tours, France, 37044
        • Local Institution - 0062
  • Greece
      • Athens, Greece, 11527
        • Local Institution - 0019
      • Thessaloniki, Greece, 57001
        • Local Institution - 0122
  • Hungary
      • Budapest, Hungary, 1125
        • Local Institution
      • Székesfehérvár, Hungary, 8000
        • Local Institution
  • Italy
      • Bari, Italy, 70124
        • Local Institution - 0068
      • Genova, Italy, 16132
        • Local Institution - 0080
      • Perugia, Italy, 06129
        • Local Institution - 0070
      • Ravenna, Italy, 48121
        • Local Institution - 0066
      • Roma, Italy, 00149
        • Local Institution - 0067
  • Japan
      • Osaka, Japan, 589-8511
        • Local Institution - 0108
      • Tokyo, Japan, 113-8603
        • Local Institution - 0124
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 4640021
        • Local Institution - 0131
    • Chiba
      • Kashiwa-shi, Chiba, Japan, 2778577
        • Local Institution - 0118
    • Fukuoka
      • Kitakyushu-shi, Fukuoka, Japan, 8078555
        • Local Institution - 0111
    • Fukushima
      • Fukushima, Fukushima, Japan, 9601295
        • Local Institution - 0110
    • Hiroshima
      • Hiroshima, Hiroshima, Japan, 7348551
        • Local Institution - 0109
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 0030804
        • Local Institution - 0147
    • Hyōgo
      • Kobe, Hyōgo, Japan, 6500047
        • Local Institution - 0133
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 2418515
        • Local Institution - 0123
    • Miyagi
      • Sendai, Miyagi, Japan, 9800873
        • Local Institution - 0148
    • Osaka
      • Osaka, Osaka, Japan, 5418567
        • Local Institution - 0127
      • Sakai-shi, Osaka, Japan, 5918555
        • Local Institution - 0119
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan, 4118777
        • Local Institution - 0132
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 1138431
        • Local Institution - 0126
      • Shinjuku-ku, Tokyo, Japan, 1600023
        • Local Institution - 0120
  • Romania
      • Craiova, Romania, 200347
        • Local Institution - 0050
      • Romania, Romania, 400015
        • Local Institution - 0051
      • Sector 2, Romania, 022328
        • Local Institution - 0069
  • South Korea
      • Busan, South Korea, 49267
        • Local Institution - 0097
      • Hwasun, South Korea, 58128
        • Local Institution - 0098
      • Seoul, South Korea, 08308
        • Local Institution - 0105
  • Spain
      • Barcelona, Spain, 08035
        • Local Institution - 0028
      • Madrid, Spain, 28041
        • Local Institution - 0029
      • Majadahonda - Madrid, Spain, 28222
        • Local Institution - 0031
  • Taiwan
      • New Taipei City, Taiwan, 235
        • Local Institution - 0102
      • Taichung, Taiwan, 407219
        • Local Institution - 0107
      • Taipei, Taiwan, 11031
        • Local Institution - 0099
      • Taipei, Taiwan, 112
        • Local Institution - 0100
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01060
        • Local Institution - 0093
      • Ankara, Turkey (Türkiye), 06100
        • Local Institution - 0084
      • Istanbul, Turkey (Türkiye), 34098
        • Local Institution - 0115
  • United States
    • Arizona
      • Glendale, Arizona, United States, 85308
        • Local Institution - 0121
    • California
      • Los Angeles, California, United States, 90017
        • Local Institution - 0081
    • Colorado
      • Denver, Colorado, United States, 80218
        • Local Institution - 0025
    • Connecticut
      • Plainville, Connecticut, United States, 06062
        • Local Institution - 0007
    • Florida
      • Hollywood, Florida, United States, 33021
        • Local Institution - 0173
      • Miami, Florida, United States, 33136
        • Local Institution - 0136
      • Orlando, Florida, United States, 32806
        • Orlando Health, Inc.
      • Orlando, Florida, United States, 32804
        • Local Institution - 0054
      • Vero Beach, Florida, United States, 32960
        • Indian River Medical Center
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Center, P.C.
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Local Institution - 0002
      • Chicago, Illinois, United States, 60611
        • Local Institution - 0015
      • Niles, Illinois, United States, 60714
        • Illinois Cancer Specialists
    • Indiana
      • Fort Wayne, Indiana, United States, 46804
        • Local Institution - 0171
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Local Institution - 0170
      • Louisville, Kentucky, United States, 40202
        • Local Institution - 0186
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • University Medical Center New Orleans
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Local Institution - 0001
      • Baltimore, Maryland, United States, 21237
        • Local Institution - 0151
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0008
      • Fairhaven, Massachusetts, United States, 02719
        • Southcoast Center For Cancer
      • Newton, Massachusetts, United States, 02459
        • Local Institution - 0006
    • Michigan
      • Detroit, Michigan, United States, 48202-2608
        • Local Institution - 0012
    • Mississippi
      • Hattiesburg, Mississippi, United States, 39401
        • Local Institution - 0090
    • Montana
      • Billings, Montana, United States, 59102
        • St Vincent Frontier Cancer Center
    • Nevada
      • Las Vegas, Nevada, United States, 89128
        • Local Institution - 0032
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Local Institution - 0009
      • Westwood, New Jersey, United States, 07675
        • Valley Hospital Luckow Pavili
    • New York
      • Albany, New York, United States, 12208
        • Local Institution - 0027
      • New York, New York, United States, 10016
        • Local Institution - 0011
    • North Carolina
      • High Point, North Carolina, United States, 27262
        • Local Institution - 0140
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Christ Hospital
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Zanesville, Ohio, United States, 43701
        • Local Institution - 0149
    • Oregon
      • Portland, Oregon, United States, 97227
        • Kaiser Permanente
      • Portland, Oregon, United States, 97239
        • Local Institution - 0139
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Local Institution - 0010
      • Pittsburgh, Pennsylvania, United States, 15212
        • Local Institution - 0018
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Local Institution - 0021
      • Charleston, South Carolina, United States, 29414
        • Local Institution - 0013
      • Greenville, South Carolina, United States, 29607
        • Local Institution - 0146
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Local Institution - 0092
      • Nashville, Tennessee, United States, 37232
        • Local Institution - 0005
    • Texas
      • Austin, Texas, United States, 78745
        • Local Institution - 0035
      • Bedford, Texas, United States, 76022
        • Texas Oncology
      • Fort Bliss, Texas, United States, 79918
        • Local Institution - 0153
      • Houston, Texas, United States, 77090
        • Local Institution - 0106
      • Lubbock, Texas, United States, 79415
        • Southwest Cancer Center
      • Sherman, Texas, United States, 75090-0504
        • Texas Cancer Center - Sherman
      • Tyler, Texas, United States, 75701
        • Local Institution - 0143
      • Waco, Texas, United States, 76712
        • Local Institution - 0026
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center
      • Salt Lake City, Utah, United States, 84112
        • Local Institution - 0003
      • St. George, Utah, United States, 84770
        • Southwest Regional Cancer Clinic
    • Vermont
      • Burlington, Vermont, United States, 05405
        • Local Institution - 0135
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Local Institution - 0125
      • Fredericksburg, Virginia, United States, 22408
        • Local Institution - 0198

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Early stage IB-IIIA, operable non-small cell lung cancer, confirmed in tissue
  • Lung function capacity capable of tolerating the proposed lung surgery
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  • Available tissue of primary lung tumor

Exclusion Criteria:

  • Presence of locally advanced, inoperable or metastatic disease
  • Participants with active, known or suspected autoimmune disease
  • Prior treatment with any drug that targets T cell co-stimulations pathways (such as checkpoint inhibitors)

Other protocol defined inclusion/exclusion criteria apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Platinum doublet chemotherapy
Specified dose on specified days
Drug: Carboplatin
Specified dose on specified days
Drug: Cisplatin
Specified dose on specified days
Drug: Paclitaxel
Specified dose on specified days
Drug: Pemetrexed
Specified dose on specified days
Drug: Docetaxel
Specified dose on specified days
Drug: Gemcitabine
Specified dose on specified days
Drug: Vinorelbine
Specified dose on specified days
Experimental: Nivolumab plus platinum doublet chemotherapy
Specified dose on specified days
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Drug: Carboplatin
Specified dose on specified days
Drug: Cisplatin
Specified dose on specified days
Drug: Paclitaxel
Specified dose on specified days
Drug: Pemetrexed
Specified dose on specified days
Drug: Gemcitabine
Specified dose on specified days
Experimental: Nivolumab plus Ipilimumab
Specified dose on specified days
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
This arm is closed and no longer enrolling patients.
Other Names:
  • BMS-734016
  • Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-Free Survival (EFS)
Time Frame: From randomization to disease progression, reoccurrence, or death due to any cause. (Up to a median of 30 months)
Event-free survival (EFS) is defined as the length of time from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on blinded independent central review (BICR) assessment per response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
From randomization to disease progression, reoccurrence, or death due to any cause. (Up to a median of 30 months)
Pathologic Complete Response (pCR) Rate
Time Frame: From randomization up to a median of 30 months after randomization.
Pathologic complete response (pCR) rate is defined as the number of randomized participants with absence of residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR).
From randomization up to a median of 30 months after randomization.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathologic Response (MPR) Rate
Time Frame: From randomization up to a median of 30 months after randomization.
Major pathologic response (MPR) rate is defined as number of randomized participants with </= 10% residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR). Viable tumors in situ carcinoma should not be included in MPR calculation.
From randomization up to a median of 30 months after randomization.
Overall Survival (OS)
Time Frame: From randomization to the date of death (Up to approximately 93 months)
Overall survival (OS) is defined as the time between the date of randomization and the date of death. OS will be censored on the last date a participant was known to be alive.
From randomization to the date of death (Up to approximately 93 months)
Time to Death or Distant Metastases (TTDM)
Time Frame: From randomization to the first date of distant metastasis or the date of death in the absence of distant metastasis (Up to approximately 84 months)
TTDM is defined as the time between the date of randomization and the first date of distant metastasis or the date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the thorax using blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Patients who have not developed distant metastasis or died at the time of analysis will be censored on the date of their last evaluable tumor assessment.
From randomization to the first date of distant metastasis or the date of death in the absence of distant metastasis (Up to approximately 84 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharmaceutical Co. Ltd

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2017

Primary Completion (Actual)

September 8, 2021

Study Completion (Actual)

December 6, 2024

Study Registration Dates

First Submitted

December 16, 2016

First Submitted That Met QC Criteria

December 16, 2016

First Posted (Estimated)

December 20, 2016

Study Record Updates

Last Update Posted (Estimated)

January 6, 2026

Last Update Submitted That Met QC Criteria

January 2, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-816
  • 2016-003536-21 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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