Clinical trial NCT02864251: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small-Cell Lung Carcinoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2016-08-11
Enrollment: 367
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS) by Blinded Independent Centralized Review (BICR)
timeFrame: From randomization to the date of first documented tumor progression or death (approximately 58 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to the date of death due to any cause (up to approximately 67 months)
measure: Objective Response Rate (ORR) by Blinded Independent Centralized Review (BICR)
timeFrame: From randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (up to approximately 67 months)
measure: Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)
timeFrame: From randomization to the date of first documented disease progression or death due to any cause (approximately 67 months)
measure: 9 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)
timeFrame: 9 months after first treatment dose
measure: 12 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)
timeFrame: 12 Months after first treatment dose
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0029
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0033
state: California
city: Orange
country: United States
facility: Local Institution - 0061
state: California
city: Redondo Beach
country: United States
facility: Torrance Memorial Physican Network
state: California
city: New Haven
country: United States
facility: Local Institution - 0003
state: Connecticut
city: Chicago
country: United States
facility: Local Institution - 0004
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0002
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Local Institution - 0064
state: New York
city: Butner
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Arlington
country: United States
facility: Texas Health Physicians Group
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Tyler
country: United States
facility: Local Institution - 0063
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 0001
state: Utah
city: Edmonton
country: Canada
facility: Local Institution - 0166
state: Alberta
city: Montreal
country: Canada
facility: Local Institution - 0168
state: Quebec
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Chongqing
country: China
facility: Local Institution
state: Chongqing
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Zhengzhou
country: China
facility: Local Institution
state: Henan
city: Hong Kong
country: China
facility: Local Institution
state: Hong Kong
city: Changsha
country: China
facility: Local Institution - 0043
state: Hunan
city: Changchun
country: China
facility: Local Institution
state: Jilin
city: Changchun
country: China
facility: Local Institution
state: Jilin
city: Xian
country: China
facility: Local Institution
state: Shan3xi
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Chengdu
country: China
facility: Local Institution
state: Sichuan
city: Hangzhou
country: China
facility: Local Institution - 0016
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 0017
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution
state: Zhejiang
city: Marseille
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution - 0156
city: Rennes
country: France
facility: Local Institution
city: Toulouse cedex 9
country: France
facility: Local Institution
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0027
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0024
city: Shatin
country: Hong Kong
facility: Local Institution
city: Nagoya-shi
country: Japan
facility: Local Institution
state: Aichi
city: Hirosaki-shi
country: Japan
facility: Local Institution
state: Aomori
city: Matsuyama
country: Japan
facility: Local Institution
state: Ehime
city: Iizuka
country: Japan
facility: Local Institution
state: Fukuoka
city: Kurume
country: Japan
facility: Local Institution - 0059
state: Fukuoka
city: Fukushima-shi
country: Japan
facility: Local Institution
state: Fukushima
city: Koriyama
country: Japan
facility: Local Institution
state: Fukushima
city: Fukuyama
country: Japan
facility: Local Institution
state: Hiroshima
city: Hiroshima-Shi
country: Japan
facility: Local Institution
state: Hiroshima
city: Sapporo
country: Japan
facility: Local Institution - 0070
state: Hokkaido
city: Himeji-shi
country: Japan
facility: Local Institution
state: Hyogo
city: Itami
country: Japan
facility: Local Institution - 0097
state: Hyogo
city: Kobe City
country: Japan
facility: Local Institution
state: Hyogo
city: Kobe
country: Japan
facility: Local Institution
state: Hyogo
city: Bunkyo-ku
country: Japan
facility: Local Institution
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Local Institution - 0081
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Local Institution
state: Kumamoto
city: Natori-shi
country: Japan
facility: Local Institution
state: Miyagi
city: Sendai-shi
country: Japan
facility: Local Institution - 0077
state: Miyagi
city: Hirakata-shi
country: Japan
facility: Local Institution
state: Osaka
city: Kishiwada shi
country: Japan
facility: Local Institution
state: Osaka
city: Osakasayama
country: Japan
facility: Local Institution - 0058
state: Osaka
city: Sakai
country: Japan
facility: Local Institution
state: Osaka
city: Hidaka
country: Japan
facility: Local Institution - 0076
state: Saitama
city: Kitaadachi-gun
country: Japan
facility: Local Institution
state: Saitama
city: Chuo
country: Japan
facility: Local Institution - 0069
state: Tokyo
city: Koto-ku
country: Japan
facility: Local Institution - 0078
state: Tokyo
city: Ube Shi
country: Japan
facility: Local Institution
state: Yamaguchi
city: Chiba
country: Japan
facility: Local Institution
city: Fukuoka
country: Japan
facility: Local Institution
city: Fukuoka
country: Japan
facility: Local Institution
city: Niigata
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution - 0079
city: Toyama
country: Japan
facility: Local Institution
city: Wakayama
country: Japan
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0038
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0037
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0035
state: Seoul Teugbyeolsi
city: Cheogju-si
country: Korea, Republic of
facility: Local Institution
city: Gyeonggi-do,
country: Korea, Republic of
facility: Local Institution
city: Gyeonggi-do
country: Korea, Republic of
facility: Local Institution - 0036
city: Inchoen
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution - 0042
city: Singapore
country: Singapore
facility: Local Institution - 0041
city: Barcelona
country: Spain
facility: Local Institution - 0158
city: Hospitalet de Llobregat
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Majadahonda
country: Spain
facility: Local Institution
city: Malaga
country: Spain
facility: Local Institution
city: Zaragoza
country: Spain
facility: Local Institution
city: Tainan
country: Taiwan
facility: Local Institution - 0021
state: TNN
city: Chiayi
country: Taiwan
facility: Local Institution - 0045
city: Kaohsiung City
country: Taiwan
facility: Local Institution
city: Kaohsiung city
country: Taiwan
facility: Local Institution
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0019
city: Taichung
country: Taiwan
facility: Local Institution - 0018
city: Taichung
country: Taiwan
facility: Local Institution
city: Tainan
country: Taiwan
facility: Local Institution
city: Taipei City
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution - 0066
city: Taipei
country: Taiwan
facility: Local Institution - 0108
city: Taipei
country: Taiwan
facility: Local Institution - 0023
city: Taoyuan
country: Taiwan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: