A Study of Nivolumab + Chemotherapy or Nivolumab + Ipilimumab Versus Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Who Failed 1L or 2L EGFR Tyrosine Kinase Inhibitor (TKI) Therapy (CheckMate722)

Open-Label, Randomized Trial of Nivolumab (BMS-936558) Plus Pemetrexed/Platinum or Nivolumab Plus Ipilimumab (BMS-734016) vs Pemetrexed Plus Platinum in Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) Subjects With Epidermal Growth Factor Receptor (EGFR) Mutation Who Failed 1L or 2L EGFR Tyrosine Kinase Inhibitor Therapy

The main purpose of this study is to determine whether nivolumab + chemotherapy is effective as compared to chemotherapy in the treatment of patients with EGFR mutation, NSCLC who failed first line (1L) or second-line (2L) EGFR TKI therapy.

Study Overview

• Status: Completed
• Conditions: Non-Small-Cell Lung Carcinoma
• Intervention / Treatment: Biological: Nivolumab; Biological: Ipilimumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 367
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0166
  • Quebec
    • Montreal, Quebec, Canada, H4A3J1
      • Local Institution - 0168
• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Local Institution
    • Beijing, Beijing, China, 100853
      • Local Institution
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Local Institution
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Local Institution
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Local Institution
  • Hong Kong
    • Hong Kong, Hong Kong, China
      • Local Institution
  • Hunan
    • Changsha, Hunan, China, 410013
      • Local Institution - 0043
  • Jilin
    • Changchun, Jilin, China, 130012
      • Local Institution
    • Changchun, Jilin, China, 130021
      • Local Institution
  • Shan3xi
    • Xian, Shan3xi, China, 710032
      • Local Institution
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Local Institution
    • Shanghai, Shanghai, China, 200030
      • Local Institution
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Local Institution
    • Hangzhou, Zhejiang, China, 310006
      • Local Institution - 0016
    • Hangzhou, Zhejiang, China, 310011
      • Local Institution - 0017
• France
  • Marseille, France, 13915
    • Local Institution
  • Paris, France, 75005
    • Local Institution - 0156
  • Rennes, France, 35033
    • Local Institution
  • Toulouse cedex 9, France, 31059
    • Local Institution
• Hong Kong
  • Hong Kong, Hong Kong
    • Local Institution - 0027
  • Hong Kong, Hong Kong
    • Local Institution - 0024
  • Shatin, Hong Kong
    • Local Institution
• Japan
  • Chiba, Japan, 2608670
    • Local Institution
  • Fukuoka, Japan, 810-0001
    • Local Institution
  • Fukuoka, Japan, 812-8582
    • Local Institution
  • Niigata, Japan, 990-9585
    • Local Institution
  • Tokyo, Japan, 1600023
    • Local Institution - 0079
  • Toyama, Japan, 930-8550
    • Local Institution
  • Wakayama, Japan, 6418510
    • Local Institution
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4648681
      • Local Institution
  • Aomori
    • Hirosaki-shi, Aomori, Japan, 036-8174
      • Local Institution
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • Local Institution
  • Fukuoka
    • Iizuka, Fukuoka, Japan, 8208505
      • Local Institution
    • Kurume, Fukuoka, Japan, 830-0011
      • Local Institution - 0059
  • Fukushima
    • Fukushima-shi, Fukushima, Japan, 9601295
      • Local Institution
    • Koriyama, Fukushima, Japan, 9630197
      • Local Institution
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 7210971
      • Local Institution
    • Hiroshima-Shi, Hiroshima, Japan, 7348551
      • Local Institution
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • Local Institution - 0070
  • Hyogo
    • Himeji-shi, Hyogo, Japan, 6708520
      • Local Institution
    • Itami, Hyogo, Japan, 6648540
      • Local Institution - 0097
    • Kobe, Hyogo, Japan, 6500047
      • Local Institution
    • Kobe City, Hyogo, Japan, 6500047
      • Local Institution
  • Kanagawa
    • Bunkyo-ku, Kanagawa, Japan, 1138603
      • Local Institution
    • Yokohama, Kanagawa, Japan, 236-0051
      • Local Institution
    • Yokohama, Kanagawa, Japan, 241-8515
      • Local Institution
    • Yokohama-shi, Kanagawa, Japan, 2210855
      • Local Institution - 0081
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 861-4193
      • Local Institution
  • Miyagi
    • Natori-shi, Miyagi, Japan, 981-1293
      • Local Institution
    • Sendai-shi, Miyagi, Japan, 9800873
      • Local Institution - 0077
  • Osaka
    • Hirakata-shi, Osaka, Japan, 573-1191
      • Local Institution
    • Kishiwada shi, Osaka, Japan, 5968501
      • Local Institution
    • Osakasayama, Osaka, Japan, 589-8511
      • Local Institution - 0058
    • Sakai, Osaka, Japan, 591-8555
      • Local Institution
  • Saitama
    • Hidaka, Saitama, Japan, 350-1298
      • Local Institution - 0076
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Local Institution
  • Tokyo
    • Chuo, Tokyo, Japan, 104-0045
      • Local Institution - 0069
    • Koto-ku, Tokyo, Japan, 1358550
      • Local Institution - 0078
  • Yamaguchi
    • Ube Shi, Yamaguchi, Japan, 7550241
      • Local Institution
• Korea, Republic of
  • Cheogju-si, Korea, Republic of, 361-711
    • Local Institution
  • Gyeonggi-do, Korea, Republic of, 463-707
    • Local Institution - 0036
  • Gyeonggi-do,, Korea, Republic of, 10408
    • Local Institution
  • Inchoen, Korea, Republic of, 405-760
    • Local Institution
  • Seoul, Korea, Republic of, 06591
    • Local Institution
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 05505
      • Local Institution - 0037
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
      • Local Institution - 0035
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Local Institution - 0038
• Singapore
  • Singapore, Singapore, 308433
    • Local Institution - 0041
  • Singapore, Singapore, 119074
    • Local Institution - 0042
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0158
  • Hospitalet de Llobregat, Spain, 08907
    • Local Institution
  • Madrid, Spain, 28041
    • Local Institution
  • Majadahonda, Spain, 28222
    • Local Institution
  • Malaga, Spain, 29010
    • Local Institution
  • Zaragoza, Spain, 50009
    • Local Institution
• Taiwan
  • Chiayi, Taiwan, 62247
    • Local Institution - 0045
  • Kaohsiung, Taiwan, 83301
    • Local Institution - 0019
  • Kaohsiung City, Taiwan, 807
    • Local Institution
  • Kaohsiung city, Taiwan, 82445
    • Local Institution
  • Taichung, Taiwan, 40705
    • Local Institution
  • Taichung, Taiwan, 40447
    • Local Institution - 0018
  • Tainan, Taiwan, 736
    • Local Institution
  • Taipei, Taiwan, 10002
    • Local Institution
  • Taipei, Taiwan, 10449
    • Local Institution - 0066
  • Taipei, Taiwan, 11031
    • Local Institution - 0108
  • Taipei, Taiwan, 112
    • Local Institution - 0023
  • Taipei City, Taiwan, 114
    • Local Institution
  • Taoyuan, Taiwan, 333
    • Local Institution
  • TNN
    • Tainan, TNN, Taiwan, 704
      • Local Institution - 0021
• United States
  • California
    • Long Beach, California, United States, 90808
      • Pacific Shores Medical Group
    • Los Angeles, California, United States, 90017
      • Local Institution - 0029
    • Los Angeles, California, United States, 90095
      • Local Institution - 0033
    • Orange, California, United States, 92868
      • Local Institution - 0061
    • Redondo Beach, California, United States, 90277
      • Torrance Memorial Physican Network
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0003
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Local Institution - 0004
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 0002
  • New York
    • New York, New York, United States, 10016
      • Local Institution - 0064
  • North Carolina
    • Butner, North Carolina, United States, 27509-1626
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Health Physicians Group
    • Temple, Texas, United States, 76508
      • Baylor Scott and White Research Institute
    • Tyler, Texas, United States, 75701
      • Local Institution - 0063
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Local Institution - 0001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed stage IV or recurrent EGFR mutated NSCLC with disease progression on one or two prior lines of treatment with EGFR TKIs (allowed TKIs must be approved by the local health authority, including but not limited to erlotinib, gefitinib, afatinib, dacomitinib and osimertinib). In osimertinib treated subjects, T790 testing is not required.
• No evidence of exon 20 T790M mutation obtained at progression on prior first- or second-generation EGFR TKI therapy. For participants who were treated with osimertinib, T790M testing is not required.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• Available tumor sample for Programmed death-ligand 1 (PD-L1) immunohistochemical (IHC).
• Participants are eligible if central nervous system (CNS) metastases are considered to be adequately controlled/treated before or during the screening period and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, participants must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization). Participants with asymptomatic CNS metastasis are eligible.
• Eastern Cooperative Group (ECOG) Performance Status 0-1
• Life expectancy is at least 3 months

Exclusion Criteria:

• Known EGFR mutation, T790M positive who failed 1L first- or second-generation TKI should receive osimertinib first as the standard of care (SOC). These participants are only eligible if they fail osimertinib as 2L.
• who have progressed within 3 months of the first dose of 1L or 2L EGFR TKI.
• Carcinomatous meningitis
• Active, known or suspected autoimmune disease are excluded
• ALK translocation
• Known SCLC transformation
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab+Platinum doublet chemotherapy	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: Pemetrexed; Specified dose on specified days
Experimental: Nivolumab + Ipilimumab; Enrollment is closed for this arm	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: Ipilimumab; Specified dose on specified days; Other Names: BMS-734016; Yervoy
Active Comparator: Platinum doublet chemotherapy	Drug: Carboplatin; Specified dose on specified days; Drug: Cisplatin; Specified dose on specified days; Drug: Pemetrexed; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by Blinded Independent Centralized Review (BICR)	PFS is defined as the time between the date of randomization and the date of first documented tumor progression, as determined by BICR (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. Participants who died without reported progression will be considered to have progressed on the date of their death. Subsequent therapy was accounted for by censoring at the last evaluable tumor assessment on or prior to the date of subsequent therapy. Progression is the appearance of one or more new lesions. RECIST - "response evaluation criteria in solid tumors" is a standard system to measure tumor response to treatment. Based on Kaplan-Meier estimates	From randomization to the date of first documented tumor progression or death (approximately 58 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
9 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)	The PFSR at 9 months is defined as the percent of treated participants remaining progression free and surviving at 9 months since the first dosing date. Progression is the appearance of one or more new lesions. Point estimates are derived from Kaplan-Meier analyses.	9 months after first treatment dose
12 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)	The PFSR at 12 months is defined as the percent of treated participants remaining progression free and surviving at 12 months since the first dosing date. Progression is the appearance of one or more new lesions. Point estimates are derived from Kaplan-Meier analyses.	12 Months after first treatment dose
Overall Survival (OS)	Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a participant was known to be alive. Median based on Kaplan-Meier Estimates	From randomization to the date of death due to any cause (up to approximately 67 months)
Objective Response Rate (ORR) by Blinded Independent Centralized Review (BICR)	ORR is number of randomized participants who have confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST v1.1 criteria by BICR assessment. BOR is the best response designation, between randomization and objectively documented progression per RECIST v1.1 criteria by BICR or the date of subsequent anti-cancer therapy, whichever occurs first. PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in the short axis of pathological lymph nodes to <10 mm (whether target or non-target). Radiographic tumor response assessments from Week 7 (± 7 days), then every 6 weeks (± 7 days) until Week 49 and every 12 weeks (± 7 days) thereafter, until disease progression, treatment discontinued, or the start of subsequent anti-cancer therapy. CR+PR, confidence interval based on the Clopper and Pearson method.	From randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (up to approximately 67 months)
Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)	DOR is the time between the date of first response (CR or PR) and the date of first documented disease progression as determined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) or death due to any cause (death occurring after re-treatment or randomization to new combination treatment was not included), whichever occurred first. PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in the short axis of pathological lymph nodes to <10 mm (whether target or non-target). Radiographic tumor response assessments from Week 7 (± 7 days), then every 6 weeks (± 7 days) until Week 49 and every 12 weeks (± 7 days) thereafter, until disease progression, treatment discontinued, or the start of subsequent anti-cancer therapy. Participants who neither progress nor die were censored on the date of their last assessment. Median computed using Kaplan-Meier method	From randomization to the date of first documented disease progression or death due to any cause (approximately 67 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2017
• Primary Completion (Actual): January 20, 2022
• Study Completion (Actual): October 17, 2022

Study Registration Dates

• First Submitted: August 9, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimated): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Nivolumab; Pemetrexed; Ipilimumab
• Other Study ID Numbers: CA209-722; 2017-002672-38 (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