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

NCT ID: NCT02998528

Last Updated: 2026-01-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

505 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-04

Study Completion Date

2024-12-06

Brief Summary

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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.

Detailed Description

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Conditions

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Non Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Platinum doublet chemotherapy

Specified dose on specified days

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Specified dose on specified days

Vinorelbine

Intervention Type DRUG

Specified dose on specified days

Gemcitabine

Intervention Type DRUG

Specified dose on specified days

Docetaxel

Intervention Type DRUG

Specified dose on specified days

Pemetrexed

Intervention Type DRUG

Specified dose on specified days

Carboplatin

Intervention Type DRUG

Specified dose on specified days

Paclitaxel

Intervention Type DRUG

Specified dose on specified days

Nivolumab plus platinum doublet chemotherapy

Specified dose on specified days

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Specified dose on specified days

Cisplatin

Intervention Type DRUG

Specified dose on specified days

Gemcitabine

Intervention Type DRUG

Specified dose on specified days

Pemetrexed

Intervention Type DRUG

Specified dose on specified days

Carboplatin

Intervention Type DRUG

Specified dose on specified days

Paclitaxel

Intervention Type DRUG

Specified dose on specified days

Nivolumab plus Ipilimumab

Specified dose on specified days

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Specified dose on specified days

Ipilimumab

Intervention Type BIOLOGICAL

This arm is closed and no longer enrolling patients.

Interventions

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Nivolumab

Specified dose on specified days

Intervention Type BIOLOGICAL

Cisplatin

Specified dose on specified days

Intervention Type DRUG

Vinorelbine

Specified dose on specified days

Intervention Type DRUG

Gemcitabine

Specified dose on specified days

Intervention Type DRUG

Docetaxel

Specified dose on specified days

Intervention Type DRUG

Pemetrexed

Specified dose on specified days

Intervention Type DRUG

Carboplatin

Specified dose on specified days

Intervention Type DRUG

Paclitaxel

Specified dose on specified days

Intervention Type DRUG

Ipilimumab

This arm is closed and no longer enrolling patients.

Intervention Type BIOLOGICAL

Other Intervention Names

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BMS-936558 Opdivo BMS-734016 Yervoy

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0121

Glendale, Arizona, United States

Site Status

Local Institution - 0081

Los Angeles, California, United States

Site Status

Local Institution - 0025

Denver, Colorado, United States

Site Status

Local Institution - 0007

Plainville, Connecticut, United States

Site Status

Local Institution - 0173

Hollywood, Florida, United States

Site Status

Local Institution - 0136

Miami, Florida, United States

Site Status

Local Institution - 0054

Orlando, Florida, United States

Site Status

Orlando Health, Inc.

Orlando, Florida, United States

Site Status

Indian River Medical Center

Vero Beach, Florida, United States

Site Status

Northwest Georgia Oncology Center, P.C.

Marietta, Georgia, United States

Site Status

Local Institution - 0015

Chicago, Illinois, United States

Site Status

Local Institution - 0002

Chicago, Illinois, United States

Site Status

Illinois Cancer Specialists

Niles, Illinois, United States

Site Status

Local Institution - 0171

Fort Wayne, Indiana, United States

Site Status

Local Institution - 0170

Lexington, Kentucky, United States

Site Status

Local Institution - 0186

Louisville, Kentucky, United States

Site Status

University Medical Center New Orleans

New Orleans, Louisiana, United States

Site Status

Local Institution - 0151

Baltimore, Maryland, United States

Site Status

Local Institution - 0001

Baltimore, Maryland, United States

Site Status

Local Institution - 0008

Boston, Massachusetts, United States

Site Status

Southcoast Center For Cancer

Fairhaven, Massachusetts, United States

Site Status

Local Institution - 0006

Newton, Massachusetts, United States

Site Status

Local Institution - 0012

Detroit, Michigan, United States

Site Status

Local Institution - 0090

Hattiesburg, Mississippi, United States

Site Status

St Vincent Frontier Cancer Center

Billings, Montana, United States

Site Status

Local Institution - 0032

Las Vegas, Nevada, United States

Site Status

Local Institution - 0009

Hackensack, New Jersey, United States

Site Status

Valley Hospital Luckow Pavili

Westwood, New Jersey, United States

Site Status

Local Institution - 0027

Albany, New York, United States

Site Status

Local Institution - 0011

New York, New York, United States

Site Status

Local Institution - 0140

High Point, North Carolina, United States

Site Status

Christ Hospital

Cincinnati, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Local Institution - 0149

Zanesville, Ohio, United States

Site Status

Kaiser Permanente

Portland, Oregon, United States

Site Status

Local Institution - 0139

Portland, Oregon, United States

Site Status

Local Institution - 0010

Philadelphia, Pennsylvania, United States

Site Status

Local Institution - 0018

Pittsburgh, Pennsylvania, United States

Site Status

Local Institution - 0013

Charleston, South Carolina, United States

Site Status

Local Institution - 0021

Charleston, South Carolina, United States

Site Status

Local Institution - 0146

Greenville, South Carolina, United States

Site Status

Local Institution - 0092

Nashville, Tennessee, United States

Site Status

Local Institution - 0005

Nashville, Tennessee, United States

Site Status

Local Institution - 0035

Austin, Texas, United States

Site Status

Texas Oncology

Bedford, Texas, United States

Site Status

Local Institution - 0153

Fort Bliss, Texas, United States

Site Status

Local Institution - 0106

Houston, Texas, United States

Site Status

Southwest Cancer Center

Lubbock, Texas, United States

Site Status

Texas Cancer Center - Sherman

Sherman, Texas, United States

Site Status

Local Institution - 0143

Tyler, Texas, United States

Site Status

Local Institution - 0026

Waco, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Local Institution - 0003

Salt Lake City, Utah, United States

Site Status

Southwest Regional Cancer Clinic

St. George, Utah, United States

Site Status

Local Institution - 0135

Burlington, Vermont, United States

Site Status

Local Institution - 0125

Fairfax, Virginia, United States

Site Status

Local Institution - 0198

Fredericksburg, Virginia, United States

Site Status

Local Institution - 0022

Capital Federal, Buenos Aires, Argentina

Site Status

Local Institution - 0023

Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina

Site Status

Local Institution - 0079

Brasília, Federal District, Brazil

Site Status

Local Institution - 0077

Belo Horizonte, Minas Gerais, Brazil

Site Status

Local Institution - 0076

Ijuí, Rio Grande do Sul, Brazil

Site Status

Local Institution - 0073

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Fundacao Pio Xii Hosp Cancer De Barretos

Barretos, São Paulo, Brazil

Site Status

Local Institution - 0075

Rio de Janeiro, , Brazil

Site Status

Local Institution - 0095

Gatineau, Quebec, Canada

Site Status

Local Institution - 0138

Montreal, Quebec, Canada

Site Status

Local Institution - 0017

Montreal, Quebec, Canada

Site Status

Local Institution - 0052

Trois-Rivières, Quebec, Canada

Site Status

Local Institution - 0016

Saskatoon, Saskatchewan, Canada

Site Status

Local Institution - 0161

Beijing, Beijing Municipality, China

Site Status

Local Institution

Beijing, Beijing Municipality, China

Site Status

Local Institution - 0156

Beijing, Beijing Municipality, China

Site Status

Local Institution - 0190

Guangzhou, Guangdong, China

Site Status

Local Institution - 0192

Changsha, Hunan, China

Site Status

Local Institution - 0175

Changsha, Hunan, China

Site Status

Local Institution - 0193

Changsha, Hunan, China

Site Status

Local Institution - 0179

Nanchang, Jiangxi, China

Site Status

Local Institution - 0166

Nanchang, Jiangxi, China

Site Status

Local Institution

Changchun, Jilin, China

Site Status

Local Institution - 0159

Xi'an, Shan1xi, China

Site Status

Local Institution - 0180

Xi'an, Shan3xi, China

Site Status

Local Institution - 0160

Shanghai, Shanghai Municipality, China

Site Status

Local Institution - 0178

Chengdu, Sichuan, China

Site Status

Local Institution - 0163

Tianjin, Tianjin Municipality, China

Site Status

Local Institution - 0189

Hangzhou, Zhejiang, China

Site Status

Local Institution - 0183

Hangzhou, Zhejiang, China

Site Status

Local Institution - 0182

Hangzhou, Zhejiang, China

Site Status

Local Institution - 0165

Shanghai, , China

Site Status

Local Institution - 0059

Marseille, , France

Site Status

Local Institution - 0060

Paris, , France

Site Status

Local Institution - 0112

Paris, , France

Site Status

Local Institution - 0064

Pierre Benite Cedax, , France

Site Status

Local Institution - 0061

Rennes, , France

Site Status

Local Institution - 0113

Strasbourg, , France

Site Status

Local Institution - 0058

Toulouse, , France

Site Status

Local Institution - 0062

Tours, , France

Site Status

Local Institution - 0019

Athens, , Greece

Site Status

Local Institution - 0122

Thessaloniki, , Greece

Site Status

Local Institution

Budapest, , Hungary

Site Status

Local Institution

Székesfehérvár, , Hungary

Site Status

Local Institution - 0068

Bari, , Italy

Site Status

Local Institution - 0080

Genova, , Italy

Site Status

Local Institution - 0070

Perugia, , Italy

Site Status

Local Institution - 0066

Ravenna, , Italy

Site Status

Local Institution - 0067

Roma, , Italy

Site Status

Local Institution - 0131

Nagoya, Aichi-ken, Japan

Site Status

Local Institution - 0118

Kashiwa-shi, Chiba, Japan

Site Status

Local Institution - 0111

Kitakyushu-shi, Fukuoka, Japan

Site Status

Local Institution - 0110

Fukushima, Fukushima, Japan

Site Status

Local Institution - 0109

Hiroshima, Hiroshima, Japan

Site Status

Local Institution - 0147

Sapporo, Hokkaido, Japan

Site Status

Local Institution - 0133

Kobe, Hyōgo, Japan

Site Status

Local Institution - 0123

Yokohama, Kanagawa, Japan

Site Status

Local Institution - 0148

Sendai, Miyagi, Japan

Site Status

Local Institution - 0127

Osaka, Osaka, Japan

Site Status

Local Institution - 0119

Sakai-shi, Osaka, Japan

Site Status

Local Institution - 0132

Sunto-gun, Shizuoka, Japan

Site Status

Local Institution - 0126

Bunkyo-ku, Tokyo, Japan

Site Status

Local Institution - 0120

Shinjuku-ku, Tokyo, Japan

Site Status

Local Institution - 0108

Osaka, , Japan

Site Status

Local Institution - 0124

Tokyo, , Japan

Site Status

Local Institution - 0050

Craiova, , Romania

Site Status

Local Institution - 0051

Romania, , Romania

Site Status

Local Institution - 0069

Sector 2, , Romania

Site Status

Local Institution - 0097

Busan, , South Korea

Site Status

Local Institution - 0098

Hwasun, , South Korea

Site Status

Local Institution - 0105

Seoul, , South Korea

Site Status

Local Institution - 0028

Barcelona, , Spain

Site Status

Local Institution - 0029

Madrid, , Spain

Site Status

Local Institution - 0031

Majadahonda - Madrid, , Spain

Site Status

Local Institution - 0102

New Taipei City, , Taiwan

Site Status

Local Institution - 0107

Taichung, , Taiwan

Site Status

Local Institution - 0099

Taipei, , Taiwan

Site Status

Local Institution - 0100

Taipei, , Taiwan

Site Status

Local Institution - 0093

Adana, , Turkey (Türkiye)

Site Status

Local Institution - 0084

Ankara, , Turkey (Türkiye)

Site Status

Local Institution - 0115

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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United States Argentina Brazil Canada China France Greece Hungary Italy Japan Romania South Korea Spain Taiwan Turkey (Türkiye)

References

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Forde PM, Spicer JD, Provencio M, Mitsudomi T, Awad MM, Wang C, Lu S, Felip E, Swanson SJ, Brahmer JR, Kerr K, Taube JM, Ciuleanu TE, Tanaka F, Saylors GB, Chen KN, Ito H, Liberman M, Martin C, Broderick S, Wang L, Cai J, Duong Q, Meadows-Shropshire S, Fiore J, Bhatia S, Girard N; CheckMate 816 Investigators. Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer. N Engl J Med. 2025 Aug 21;393(8):741-752. doi: 10.1056/NEJMoa2502931. Epub 2025 Jun 2.

Reference Type DERIVED
PMID: 40454642 (View on PubMed)

Awad MM, Forde PM, Girard N, Spicer J, Wang C, Lu S, Mitsudomi T, Felip E, Broderick SR, Swanson SJ, Brahmer J, Kerr K, Saylors GB, Chen KN, Gharpure V, Neely J, Balli D, Hu N, Provencio Pulla M. Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer. J Clin Oncol. 2025 Apr 20;43(12):1453-1462. doi: 10.1200/JCO-24-02239. Epub 2025 Jan 8.

Reference Type DERIVED
PMID: 39778121 (View on PubMed)

Deutsch JS, Cimino-Mathews A, Thompson E, Provencio M, Forde PM, Spicer J, Girard N, Wang D, Anders RA, Gabrielson E, Illei P, Jedrych J, Danilova L, Sunshine J, Kerr KM, Tran M, Bushong J, Cai J, Devas V, Neely J, Balli D, Cottrell TR, Baras AS, Taube JM. Association between pathologic response and survival after neoadjuvant therapy in lung cancer. Nat Med. 2024 Jan;30(1):218-228. doi: 10.1038/s41591-023-02660-6. Epub 2023 Oct 30.

Reference Type DERIVED
PMID: 37903504 (View on PubMed)

Akinboro O, Drezner N, Amatya A, Runyan J, Fourie-Zirkelbach J, Zhao M, Bi Y, Korsah K, Mixter B, Tang S, Larkins E, Pazdur R, Beaver JA, Singh H. US Food and Drug Administration Approval Summary: Nivolumab Plus Platinum-Doublet Chemotherapy for the Neoadjuvant Treatment of Patients With Resectable Non-Small-Cell Lung Cancer. J Clin Oncol. 2023 Jun 10;41(17):3249-3259. doi: 10.1200/JCO.22.02509. Epub 2023 May 4.

Reference Type DERIVED
PMID: 37141544 (View on PubMed)

Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N. Plain language summary of the CheckMate 816 study results: nivolumab plus chemotherapy given before surgery for non-small-cell lung cancer. Future Oncol. 2023 Mar;19(8):549-557. doi: 10.2217/fon-2023-0007. Epub 2023 Feb 23.

Reference Type DERIVED
PMID: 36815433 (View on PubMed)

Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.

Reference Type DERIVED
PMID: 35403841 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2016-003536-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-816

Identifier Type: -

Identifier Source: org_study_id

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