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

Non-Small-Cell Lung Carcinoma Clinical Trial

— CheckMate722  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02864251
• Other study ID #: CA209-722
• Secondary ID: 2017-002672-38
• Status: Completed
• Phase: Phase 3
• Start date: March 17, 2017
• Est. completion date: October 17, 2022

Study information

• Verified date: September 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 367
• Est. completion date: October 17, 2022
• Est. primary completion date: January 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Small-Cell Lung Carcinoma

Intervention

Biological:
• Nivolumab
Specified dose on specified days
• Ipilimumab
Specified dose on specified days

Drug:
• Pemetrexed
Specified dose on specified days
• Cisplatin
Specified dose on specified days
• Carboplatin
Specified dose on specified days

Locations

Country	Name	City	State
Canada	Local Institution - 0166	Edmonton	Alberta
Canada	Local Institution - 0168	Montreal	Quebec
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Changchun	Jilin
China	Local Institution	Changchun	Jilin
China	Local Institution - 0043	Changsha	Hunan
China	Local Institution	Chengdu	Sichuan
China	Local Institution	Chongqing	Chongqing
China	Local Institution	Guangzhou	Guangdong
China	Local Institution	Hangzhou	Zhejiang
China	Local Institution - 0016	Hangzhou	Zhejiang
China	Local Institution - 0017	Hangzhou	Zhejiang
China	Local Institution	Hong Kong	Hong Kong
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Xian	Shan3xi
China	Local Institution	Zhengzhou	Henan
France	Local Institution	Marseille
France	Local Institution - 0156	Paris
France	Local Institution	Rennes
France	Local Institution	Toulouse cedex 9
Hong Kong	Local Institution - 0024	Hong Kong
Hong Kong	Local Institution - 0027	Hong Kong
Hong Kong	Local Institution	Shatin
Japan	Local Institution	Bunkyo-ku	Kanagawa
Japan	Local Institution	Chiba
Japan	Local Institution - 0069	Chuo	Tokyo
Japan	Local Institution	Fukuoka
Japan	Local Institution	Fukuoka
Japan	Local Institution	Fukushima-shi	Fukushima
Japan	Local Institution	Fukuyama	Hiroshima
Japan	Local Institution - 0076	Hidaka	Saitama
Japan	Local Institution	Himeji-shi	Hyogo
Japan	Local Institution	Hirakata-shi	Osaka
Japan	Local Institution	Hirosaki-shi	Aomori
Japan	Local Institution	Hiroshima-Shi	Hiroshima
Japan	Local Institution	Iizuka	Fukuoka
Japan	Local Institution - 0097	Itami	Hyogo
Japan	Local Institution	Kishiwada shi	Osaka
Japan	Local Institution	Kitaadachi-gun	Saitama
Japan	Local Institution	Kobe	Hyogo
Japan	Local Institution	Kobe City	Hyogo
Japan	Local Institution	Koriyama	Fukushima
Japan	Local Institution - 0078	Koto-ku	Tokyo
Japan	Local Institution	Kumamoto-shi	Kumamoto
Japan	Local Institution - 0059	Kurume	Fukuoka
Japan	Local Institution	Matsuyama	Ehime
Japan	Local Institution	Nagoya-shi	Aichi
Japan	Local Institution	Natori-shi	Miyagi
Japan	Local Institution	Niigata
Japan	Local Institution - 0058	Osakasayama	Osaka
Japan	Local Institution	Sakai	Osaka
Japan	Local Institution - 0070	Sapporo	Hokkaido
Japan	Local Institution - 0077	Sendai-shi	Miyagi
Japan	Local Institution - 0079	Tokyo
Japan	Local Institution	Toyama
Japan	Local Institution	Ube Shi	Yamaguchi
Japan	Local Institution	Wakayama
Japan	Local Institution	Yokohama	Kanagawa
Japan	Local Institution	Yokohama	Kanagawa
Japan	Local Institution - 0081	Yokohama-shi	Kanagawa
Korea, Republic of	Local Institution	Cheogju-si
Korea, Republic of	Local Institution - 0036	Gyeonggi-do
Korea, Republic of	Local Institution	Gyeonggi-do,
Korea, Republic of	Local Institution	Inchoen
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution - 0035	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Local Institution - 0037	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Local Institution - 0038	Seoul	Seoul Teugbyeolsi
Singapore	Local Institution - 0041	Singapore
Singapore	Local Institution - 0042	Singapore
Spain	Local Institution - 0158	Barcelona
Spain	Local Institution	Hospitalet de Llobregat
Spain	Local Institution	Madrid
Spain	Local Institution	Majadahonda
Spain	Local Institution	Malaga
Spain	Local Institution	Zaragoza
Taiwan	Local Institution - 0045	Chiayi
Taiwan	Local Institution - 0019	Kaohsiung
Taiwan	Local Institution	Kaohsiung City
Taiwan	Local Institution	Kaohsiung city
Taiwan	Local Institution	Taichung
Taiwan	Local Institution - 0018	Taichung
Taiwan	Local Institution	Tainan
Taiwan	Local Institution - 0021	Tainan	TNN
Taiwan	Local Institution	Taipei
Taiwan	Local Institution - 0023	Taipei
Taiwan	Local Institution - 0066	Taipei
Taiwan	Local Institution - 0108	Taipei
Taiwan	Local Institution	Taipei City
Taiwan	Local Institution	Taoyuan
United States	Texas Health Physicians Group	Arlington	Texas
United States	Johns Hopkins University	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Local Institution - 0002	Boston	Massachusetts
United States	Duke University Medical Center	Butner	North Carolina
United States	Local Institution - 0004	Chicago	Illinois
United States	Pacific Shores Medical Group	Long Beach	California
United States	Local Institution - 0029	Los Angeles	California
United States	Local Institution - 0033	Los Angeles	California
United States	Local Institution - 0003	New Haven	Connecticut
United States	Local Institution - 0064	New York	New York
United States	Local Institution - 0061	Orange	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Torrance Memorial Physican Network	Redondo Beach	California
United States	Local Institution - 0001	Salt Lake City	Utah
United States	Baylor Scott and White Research Institute	Temple	Texas
United States	Local Institution - 0063	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Hong Kong,  Japan,  Korea, Republic of,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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

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